rs149174992

Variant names:

• chr15-32629647-G-C
• NM_014783.6:c.990G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-32629647-G-C
• chr15-32629647-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014783.6(ARHGAP11A):​c.990G>C​(p.Leu330Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 27)
• Consequence: ARHGAP11A NM_014783.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950

Genes affected

ARHGAP11A (HGNC:15783): (Rho GTPase activating protein 11A) This gene encodes a member of the Rho GTPase activating protein family. In response to DNA damage, the encoded protein interacts with the p53 tumor suppressor protein and stimulates its tetramerization, which results in cell-cycle arrest and apoptosis. A chromosomal deletion that includes this gene is one cause of Prader-Willi syndrome, and an intronic variant of this gene may be associated with sleep duration in children. This gene is highly expressed in colon cancers and in a human basal-like breast cancer cell line. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 (HGNC:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ENSG00000285948 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37635082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP11A	NM_014783.6	c.990G>C	p.Leu330Phe	missense_variant	Exon 8 of 12	ENST00000361627.8	NP_055598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP11A	ENST00000361627.8	c.990G>C	p.Leu330Phe	missense_variant	Exon 8 of 12	1	NM_014783.6	ENSP00000355090.3
ARHGAP11A-SCG5	ENST00000692248.1	c.990G>C	p.Leu330Phe	missense_variant	Exon 8 of 14			ENSP00000510771.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	.;T;.;.;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.78	.;T;T;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.5	.;M;M;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	N;N;N;N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.017	D;D;T;T;D
Sift4G	Uncertain	0.033	D;D;T;T;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.53
MutPred		0.18		.;Gain of methylation at K327 (P = 0.0565);Gain of methylation at K327 (P = 0.0565);Gain of methylation at K327 (P = 0.0565);.;
MVP		0.92
MPC		0.24
ClinPred		0.96	D
GERP RS		-0.33
Varity_R		0.056
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-32921848;