rs587777656

chr16-30736616-C-Achr16-30736616-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_006662.3(SRCAP):c.7000C>A(p.Gln2334Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRCAP NM_006662.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SRCAP
• BP4: Computational evidence support a benign effect (MetaRNN=0.23426482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRCAP	NM_006662.3	c.7000C>A	p.Gln2334Lys	missense_variant	33/34	ENST00000262518.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRCAP	ENST00000262518.9	c.7000C>A	p.Gln2334Lys	missense_variant	33/34	2	NM_006662.3	P1
SRCAP	ENST00000411466.7	c.7000C>A	p.Gln2334Lys	missense_variant	33/34	3		P1
SRCAP	ENST00000706321.1	c.7000C>A	p.Gln2334Lys	missense_variant	33/34			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
Cadd	Uncertain	24
Dann	Benign	0.95
DEOGEN2	Benign	0.052	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	0.92	N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.027	D;.
Sift4G	Benign	0.27	T;T
Polyphen		0.95	P;.
Vest4		0.34
MutPred		0.33		Gain of ubiquitination at Q2334 (P = 0.0082);.;
MVP		0.41
MPC		0.59
ClinPred		0.82	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs587777656; hg19: chr16-30747937;