NM_014783.6:c.1355C>G

Variant names:

• chr15-32635787-C-G
• rs146176251
• NM_014783.6:c.1355C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014783.6(ARHGAP11A):​c.1355C>G​(p.Ser452Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,597,054 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (2 hom.)
• Consequence: ARHGAP11A NM_014783.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 2 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]

ENSG00000285948 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053740144).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP11A	NM_014783.6	MANE Select	c.1355C>G	p.Ser452Cys	missense	Exon 11 of 12	NP_055598.1
	ARHGAP11A	NM_001286479.3		c.788C>G	p.Ser263Cys	missense	Exon 11 of 12	NP_001273408.1
	ARHGAP11A	NM_001286480.3		c.788C>G	p.Ser263Cys	missense	Exon 12 of 13	NP_001273409.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP11A	ENST00000361627.8	TSL:1 MANE Select	c.1355C>G	p.Ser452Cys	missense	Exon 11 of 12	ENSP00000355090.3
	ARHGAP11A	ENST00000567348.5	TSL:1	c.1355C>G	p.Ser452Cys	missense	Exon 11 of 11	ENSP00000454575.1
	ARHGAP11A-SCG5	ENST00000692248.1		c.1235+2679C>G		intron	N/A	ENSP00000510771.1

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 570 AN: 151548 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00100 AC: 240 AN: 239390 AF XY: 0.000555

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000796

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000273

Gnomad OTH exome AF: 0.000345

GnomAD4 exome AF: 0.000400 AC: 578 AN: 1445396 Hom.: 2 Cov.: 31 AF XY: 0.000337 AC XY: 242 AN XY: 718902

African (AFR) AF: 0.0130 AC: 424 AN: 32668

American (AMR) AF: 0.000841 AC: 35 AN: 41608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25704

East Asian (EAS) AF: 0.00 AC: 0 AN: 38882

South Asian (SAS) AF: 0.0000964 AC: 8 AN: 83006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.00146 AC: 8 AN: 5474

European-Non Finnish (NFE) AF: 0.0000262 AC: 29 AN: 1105302

Other (OTH) AF: 0.00124 AC: 74 AN: 59608

GnomAD4 genome AF: 0.00376 AC: 570 AN: 151658 Hom.: 3 Cov.: 33 AF XY: 0.00358 AC XY: 265 AN XY: 74062

African (AFR) AF: 0.0129 AC: 534 AN: 41338

American (AMR) AF: 0.00151 AC: 23 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67930

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.00451

ESP6500AA AF: 0.0145 AC: 64

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00122 AC: 148

Asia WGS AF: 0.000289 AC: 1 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.3
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.25
MVP		0.65
MPC		0.040
ClinPred		0.044	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.16
Mutation Taster		=99/1	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: rs146176251; hg19: chr15-32927988;