rs150246733

Variant names:

• chr16-30722724-A-G
• rs150246733
• NM_006662.3:c.3868A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006662.3(SRCAP):​c.3868A>G​(p.Ser1290Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,612,270 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00084 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (7 hom.)
• Consequence: SRCAP NM_006662.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.42
• Publications: 8 publications found

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

ENSG00000282034 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070759654).
• BP6: Variant 16-30722724-A-G is Benign according to our data. Variant chr16-30722724-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 218689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000776 (1133/1460638) while in subpopulation MID AF = 0.0123 (71/5762). AF 95% confidence interval is 0.01. There are 7 homozygotes in GnomAdExome4. There are 587 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 127 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.3868A>G	p.Ser1290Gly	missense	Exon 23 of 34	NP_006653.2	Q6ZRS2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	ENST00000262518.9	TSL:2 MANE Select	c.3868A>G	p.Ser1290Gly	missense	Exon 23 of 34	ENSP00000262518.4	Q6ZRS2-1
	ENSG00000282034	ENST00000380361.7	TSL:2	n.3362-239A>G		intron	N/A	ENSP00000369719.3	A0A0C4DFX4
	SRCAP	ENST00000411466.7	TSL:3	c.3868A>G	p.Ser1290Gly	missense	Exon 23 of 34	ENSP00000405186.3	C9J4U4

Frequencies

GnomAD3 genomes AF: 0.000838 AC: 127 AN: 151514 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000972

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00171

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000707

Gnomad OTH AF: 0.00241

GnomAD2 exomes AF: 0.00115 AC: 285 AN: 248300 AF XY: 0.00123

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000792

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.000776 AC: 1133 AN: 1460638 Hom.: 7 Cov.: 33 AF XY: 0.000808 AC XY: 587 AN XY: 726426

African (AFR) AF: 0.000717 AC: 24 AN: 33460

American (AMR) AF: 0.00170 AC: 76 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 288 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.0123 AC: 71 AN: 5762

European-Non Finnish (NFE) AF: 0.000507 AC: 563 AN: 1111152

Other (OTH) AF: 0.00162 AC: 98 AN: 60344

GnomAD4 genome AF: 0.000838 AC: 127 AN: 151632 Hom.: 0 Cov.: 32 AF XY: 0.000864 AC XY: 64 AN XY: 74092

African (AFR) AF: 0.0000969 AC: 4 AN: 41294

American (AMR) AF: 0.00170 AC: 26 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000707 AC: 48 AN: 67904

Other (OTH) AF: 0.00238 AC: 5 AN: 2098

Alfa AF: 0.00122 Hom.: 4

Bravo AF: 0.000933

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00107 AC: 9

ExAC AF: 0.000694 AC: 84

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.0025
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.23
Sift	Uncertain	0.012	D
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.37
MVP		0.20
MPC		0.16
ClinPred		0.020	T
GERP RS		5.2
Varity_R		0.17
gMVP		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150246733; hg19: chr16-30734045;