15-32620132-A-C

Variant names:

• chr15-32620132-A-C
• rs2053259743
• NM_014783.6:c.154A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014783.6(ARHGAP11A):​c.154A>C​(p.Asn52His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ARHGAP11A NM_014783.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087307006).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014783.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP11A	NM_014783.6	MANE Select	c.154A>C	p.Asn52His	missense	Exon 2 of 12	NP_055598.1	Q6P4F7-1
	ARHGAP11A-SCG5	NM_001368319.1		c.154A>C	p.Asn52His	missense	Exon 2 of 14	NP_001355248.1	A0A8I5KWH8
	ARHGAP11A	NM_199357.3		c.154A>C	p.Asn52His	missense	Exon 2 of 11	NP_955389.1	Q6P4F7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP11A	ENST00000361627.8	TSL:1 MANE Select	c.154A>C	p.Asn52His	missense	Exon 2 of 12	ENSP00000355090.3	Q6P4F7-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.154A>C	p.Asn52His	missense	Exon 2 of 14	ENSP00000510771.1	A0A8I5KWH8
	ARHGAP11A	ENST00000567348.5	TSL:1	c.154A>C	p.Asn52His	missense	Exon 2 of 11	ENSP00000454575.1	Q6P4F7-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459348 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725810

African (AFR) AF: 0.00 AC: 0 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110580

Other (OTH) AF: 0.00 AC: 0 AN: 60256

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.39	N
PhyloP100		1.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.091
Sift	Benign	0.89	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.32		Gain of catalytic residue at L54 (P = 0.073)
MVP		0.44
MPC		1.2
ClinPred		0.092	T
GERP RS		3.6
Varity_R		0.057
gMVP		0.30
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs2053259743; hg19: chr15-32912333;