chr16-30700843-C-G

Variant names:

• chr16-30700843-C-G
• rs775689955
• NM_006662.3:c.19C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006662.3(SRCAP):​c.19C>G​(p.Pro7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 0.541

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068326026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRCAP	NM_006662.3	c.19C>G	p.Pro7Ala	missense_variant	Exon 3 of 34	ENST00000262518.9	NP_006653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9	c.19C>G	p.Pro7Ala	missense_variant	Exon 3 of 34	2	NM_006662.3	ENSP00000262518.4
SRCAP	ENST00000411466.7	c.19C>G	p.Pro7Ala	missense_variant	Exon 3 of 34	3		ENSP00000405186.3
SRCAP	ENST00000706321.1	c.19C>G	p.Pro7Ala	missense_variant	Exon 3 of 34			ENSP00000516346.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.81
DEOGEN2	Benign	0.035	.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.0	.;L
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.0	D;N
REVEL	Benign	0.22
Sift	Benign	0.039	D;D
Sift4G	Benign	0.071	T;T
Polyphen		0.043	.;B
Vest4		0.12
MutPred		0.099		Loss of glycosylation at P7 (P = 0.0082);Loss of glycosylation at P7 (P = 0.0082);
MVP		0.043
MPC		0.011
ClinPred		0.10	T
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.067
gMVP		0.18

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: rs775689955; hg19: chr16-30712164;