rs181491375

chr16-30724724-C-Gchr16-30724724-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP4_Moderate

The NM_006662.3(SRCAP):c.5300C>G(p.Thr1767Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,022 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. T1767M) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SRCAP NM_006662.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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 Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SRCAP
• BP4: Computational evidence support a benign effect (MetaRNN=0.19371325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRCAP	NM_006662.3	c.5300C>G	p.Thr1767Arg	missense_variant	25/34	ENST00000262518.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRCAP	ENST00000262518.9	c.5300C>G	p.Thr1767Arg	missense_variant	25/34	2	NM_006662.3	P1
SRCAP	ENST00000411466.7	c.5300C>G	p.Thr1767Arg	missense_variant	25/34	3		P1
SRCAP	ENST00000706321.1	c.5300C>G	p.Thr1767Arg	missense_variant	25/34			P1
SRCAP	ENST00000483083.3	c.4400C>G	p.Thr1467Arg	missense_variant	18/18	2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461788 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74382

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00000479 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
Cadd	Benign	21
Dann	Benign	0.90
DEOGEN2	Benign	0.039	T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	0.90	N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.47	T;T
Polyphen		0.99	D;.
Vest4		0.47
MutPred		0.24		Loss of glycosylation at T1767 (P = 0.0086);.;
MVP		0.28
MPC		0.68
ClinPred		0.58	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.42

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: rs181491375; hg19: chr16-30736045;