rs587784443

Positions:

• chr16-30724727-T-A
• chr16-30724727-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006662.3(SRCAP):​c.5303T>A​(p.Leu1768Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 1.18

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]

ENSG00000282034 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRCAP	NM_006662.3	c.5303T>A	p.Leu1768Gln	missense_variant	25/34	ENST00000262518.9	NP_006653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9	c.5303T>A	p.Leu1768Gln	missense_variant	25/34	2	NM_006662.3	ENSP00000262518.4
ENSG00000282034	ENST00000380361.7	n.4772T>A		non_coding_transcript_exon_variant	20/31	2		ENSP00000369719.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249696 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135080

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	0.092
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.85	D;T
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N;.
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.29	T;T
Polyphen		0.79	P;.
Vest4		0.74
MutPred		0.14		Loss of sheet (P = 0.0457);.;
MVP		0.87
MPC		0.72
ClinPred		0.40	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs587784443; hg19: chr16-30736048;