16-30738522-C-G

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.8482C>G(p.Arg2828Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2828C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SRCAP NM_006662.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53

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=0.17184657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRCAP	NM_006662.3	c.8482C>G	p.Arg2828Gly	missense_variant	34/34	ENST00000262518.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRCAP	ENST00000262518.9	c.8482C>G	p.Arg2828Gly	missense_variant	34/34	2	NM_006662.3	P1
SRCAP	ENST00000411466.7	c.8482C>G	p.Arg2828Gly	missense_variant	34/34	3		P1
SRCAP	ENST00000706321.1	c.8482C>G	p.Arg2828Gly	missense_variant	34/34			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248860 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134628

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459752 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.11
Cadd	Benign	19
Dann	Benign	0.76
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.96	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N;.
REVEL	Uncertain	0.34
Sift	Benign	0.13	T;.
Sift4G	Benign	0.26	T;T
Polyphen		0.39	B;.
Vest4		0.47
MutPred		0.34		Gain of sheet (P = 0.0477);.;
MVP		0.24
MPC		0.23
ClinPred		0.14	T
GERP RS		4.3
Varity_R		0.083
gMVP		0.46

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: rs144623507; hg19: chr16-30749843;