chrX-102937494-A-G

Variant names:

• chrX-102937494-A-G
• rs145606134
• NM_001031834.1:c.176A>G

Variant summary

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

The NM_001031834.1(RAB40AL):​c.176A>G​(p.Asp59Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,210,129 control chromosomes in the GnomAD database, including 18 homozygotes. There are 2,285 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., 150 hem., cov: 22)
  • Exomes 𝑓: 0.0057 (16 hom. 2135 hem.)
• Consequence: RAB40AL NM_001031834.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 3.12
• Publications: 14 publications found

Genes affected

RAB40AL (HGNC:25410): (RAB40A like) This gene encodes a member of the Rab40 subfamily of Rab small GTP-binding proteins that contains a C-terminal suppressors of cytokine signaling box. Disruptions in this gene are associated with Duchenne muscular dystrophy. [provided by RefSeq, Apr 2010]

LINC00630 (HGNC:44263): (long intergenic non-protein coding RNA 630)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.013548255).
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031834.1. 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
	RAB40AL	NM_001031834.1	MANE Select	c.176A>G	p.Asp59Gly	missense	Exon 1 of 1	NP_001027004.1
	LINC00630	NR_146589.1		n.1910-21154A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40AL	ENST00000218249.7	TSL:6 MANE Select	c.176A>G	p.Asp59Gly	missense	Exon 1 of 1	ENSP00000218249.5
	LINC00630	ENST00000420471.6	TSL:3	n.1747+31757A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00409 AC: 457 AN: 111842 Hom.: 2 Cov.: 22

Gnomad AFR AF: 0.000554

Gnomad AMI AF: 0.00293

Gnomad AMR AF: 0.00357

Gnomad ASJ AF: 0.0348

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00267

Gnomad FIN AF: 0.00145

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.00527

Gnomad OTH AF: 0.00732

GnomAD2 exomes AF: 0.00539 AC: 989 AN: 183454 AF XY: 0.00575

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.00233

Gnomad ASJ exome AF: 0.0348

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00156

Gnomad NFE exome AF: 0.00635

Gnomad OTH exome AF: 0.00729

GnomAD4 exome AF: 0.00572 AC: 6278 AN: 1098235 Hom.: 16 Cov.: 32 AF XY: 0.00587 AC XY: 2135 AN XY: 363589

African (AFR) AF: 0.000871 AC: 23 AN: 26403

American (AMR) AF: 0.00207 AC: 73 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 659 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00375 AC: 203 AN: 54146

European-Finnish (FIN) AF: 0.00192 AC: 78 AN: 40533

Middle Eastern (MID) AF: 0.0116 AC: 48 AN: 4135

European-Non Finnish (NFE) AF: 0.00583 AC: 4909 AN: 842128

Other (OTH) AF: 0.00618 AC: 285 AN: 46094

GnomAD4 genome AF: 0.00408 AC: 457 AN: 111894 Hom.: 2 Cov.: 22 AF XY: 0.00440 AC XY: 150 AN XY: 34076

African (AFR) AF: 0.000553 AC: 17 AN: 30733

American (AMR) AF: 0.00356 AC: 38 AN: 10662

Ashkenazi Jewish (ASJ) AF: 0.0348 AC: 92 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3521

South Asian (SAS) AF: 0.00268 AC: 7 AN: 2610

European-Finnish (FIN) AF: 0.00145 AC: 9 AN: 6193

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.00527 AC: 280 AN: 53106

Other (OTH) AF: 0.00723 AC: 11 AN: 1522

Alfa AF: 0.00588 Hom.: 88

Bravo AF: 0.00404

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.00479 AC: 581

EpiCase AF: 0.00665

EpiControl AF: 0.00777

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Deafness-intellectual disability, Martin-Probst type syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.014	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.1
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.11
MVP		0.95
MPC		1.4
ClinPred		0.053	T
GERP RS		0.78
PromoterAI		0.018	Neutral
Varity_R		0.87
gMVP		0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs145606134; hg19: chrX-102192422; COSMIC: COSV54434474; COSMIC: COSV54434474;