16-30722724-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006662.3(SRCAP):ā€‹c.3868A>Gā€‹(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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00084 ( 0 hom., cov: 32)
Exomes š‘“: 0.00078 ( 7 hom. )

Consequence

SRCAP
NM_006662.3 missense

Scores

3
16

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 218689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30722724-A-G is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 587 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 127 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SRCAPNM_006662.3 linkc.3868A>G p.Ser1290Gly missense_variant 23/34 ENST00000262518.9 NP_006653.2 Q6ZRS2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SRCAPENST00000262518.9 linkc.3868A>G p.Ser1290Gly missense_variant 23/342 NM_006662.3 ENSP00000262518.4 Q6ZRS2-1
ENSG00000282034ENST00000380361.7 linkn.3362-239A>G intron_variant 2 ENSP00000369719.3 A0A0C4DFX4

Frequencies

GnomAD3 genomes
AF:
0.000838
AC:
127
AN:
151514
Hom.:
0
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00115
AC:
285
AN:
248300
Hom.:
3
AF XY:
0.00123
AC XY:
166
AN XY:
134694
show subpopulations
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 SAS exome
AF:
0.000164
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
show subpopulations
Gnomad4 AFR exome
AF:
0.000717
Gnomad4 AMR exome
AF:
0.00170
Gnomad4 ASJ exome
AF:
0.0111
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000507
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
AF:
0.000838
AC:
127
AN:
151632
Hom.:
0
Cov.:
32
AF XY:
0.000864
AC XY:
64
AN XY:
74092
show subpopulations
Gnomad4 AFR
AF:
0.0000969
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.0115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000707
Gnomad4 OTH
AF:
0.00238
Alfa
AF:
0.00130
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

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2024SRCAP: BS1, BS2 -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsMay 24, 2017- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 01, 2024- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingGenomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of PhiladelphiaJul 17, 2015- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 15, 2018- -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150246733; hg19: chr16-30734045; API