rs143519723

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006662.3(SRCAP):c.3388C>T(p.Pro1130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,614,170 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 19 hom. )

Consequence

SRCAP
NM_006662.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.66

Publications

8 publications found

Variant links:

Genes affected

SRCAP (HGNC:16974): (Snf2 related CREBBP activator protein) This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

SRCAP Gene-Disease associations (from GenCC):

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
Floating-Harbor syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

SRCAP links:

ENSG00000282034 (HGNC:):

ENSG00000282034 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008159697).

BP6

Variant 16-30721323-C-T is Benign according to our data. Variant chr16-30721323-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 195606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00285 (434/152344) while in subpopulation AMR AF = 0.00575 (88/15302). AF 95% confidence interval is 0.00478. There are 0 homozygotes in GnomAd4. There are 214 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 434 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	NM_006662.3	MANE Select	c.3388C>T	p.Pro1130Ser	missense	Exon 21 of 34	NP_006653.2	Q6ZRS2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRCAP	ENST00000262518.9	TSL:2 MANE Select	c.3388C>T	p.Pro1130Ser	missense	Exon 21 of 34	ENSP00000262518.4	Q6ZRS2-1
ENSG00000282034	ENST00000380361.7	TSL:2	n.3196+345C>T		intron	N/A	ENSP00000369719.3	A0A0C4DFX4
SRCAP	ENST00000411466.7	TSL:3	c.3388C>T	p.Pro1130Ser	missense	Exon 21 of 34	ENSP00000405186.3	C9J4U4

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00287

AC:

722

AN:

251382

AF XY:

0.00279

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00403

AC:

5888

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

2844

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

33480

American (AMR)

AF:

0.00436

AC:

195

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00247

AC:

213

AN:

86258

European-Finnish (FIN)

AF:

0.00189

AC:

101

AN:

53352

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00461

AC:

5127

AN:

1112012

Other (OTH)

AF:

0.00306

AC:

185

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

386

771

1157

1542

1928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

206

412

618

824

1030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00285

AC:

434

AN:

152344

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41578

American (AMR)

AF:

0.00575

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00226

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00387

AC:

263

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00343

Hom.:

Bravo

AF:

0.00293

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00257

AC:

312

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00332

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.054

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0082

MetaSVM

Uncertain

0.41

MutationAssessor

Benign

0.90

PhyloP100

1.7

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Benign

0.11

Polyphen

0.98

Vest4

0.47

MVP

0.26

MPC

0.54

ClinPred

0.022

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.22

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over