X-102937553-A-G

Position:

• chrX-102937553-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031834.1(RAB40AL):​c.235A>G​(p.Ile79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,849 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: RAB40AL NM_001031834.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB40AL	NM_001031834.1	c.235A>G	p.Ile79Val	missense_variant	1/1	ENST00000218249.7	NP_001027004.1
LINC00630	NR_146589.1	n.1910-21095A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40AL	ENST00000218249.7	c.235A>G	p.Ile79Val	missense_variant	1/1	6	NM_001031834.1	ENSP00000218249.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097849 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363223

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deafness-intellectual disability, Martin-Probst type syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centogene AG - the Rare Disease Company

Apr 22, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.20	T
Polyphen		0.69	P
Vest4		0.39
MutPred		0.73		Gain of methylation at R75 (P = 0.1167);
MVP		0.82
MPC		1.2
ClinPred		0.74	D
GERP RS		0.61
Varity_R		0.28
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs2084562831; hg19: chrX-102192481;