X-102937320-T-C

Variant names:

• chrX-102937320-T-C
• rs767350323
• NM_001031834.1:c.2T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001031834.1(RAB40AL):​c.2T>C​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: RAB40AL NM_001031834.1 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.09
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 105 codons. Genomic position: 102937631. Lost 0.374 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40AL	NM_001031834.1	MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 1	NP_001027004.1	P0C0E4
	LINC00630	NR_146589.1		n.1910-21328T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40AL	ENST00000218249.7	TSL:6 MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 1	ENSP00000218249.5	P0C0E4
	LINC00630	ENST00000420471.6	TSL:3	n.1747+31583T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000559 AC: 1 AN: 178943 AF XY: 0.0000156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Uncertain	0.0
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0044	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.26	T
PhyloP100		5.1
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.32
MutPred		0.98		Gain of glycosylation at M1 (P = 0.002)
MVP		0.96
ClinPred		0.98	D
GERP RS		0.99
PromoterAI		0.19	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.90
gMVP		0.63
Mutation Taster		=103/97	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: rs767350323; hg19: chrX-102192248;