X-32468692-G-C

Position:

• chrX-32468692-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004006.3(DMD):​c.2968C>G​(p.Gln990Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 111,419 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 22)
• Consequence: DMD NM_004006.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12687272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.2968C>G	p.Gln990Glu	missense_variant	23/79	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.2968C>G	p.Gln990Glu	missense_variant	23/79	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.00000898 AC: 1 AN: 111419 Hom.: 0 Cov.: 22 AF XY: 0.0000297 AC XY: 1 AN XY: 33619

Gnomad AFR AF: 0.0000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000898 AC: 1 AN: 111419 Hom.: 0 Cov.: 22 AF XY: 0.0000297 AC XY: 1 AN XY: 33619

Gnomad4 AFR AF: 0.0000326

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.50
DEOGEN2	Benign	0.20	.;T;.;.
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;.;D;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.37	.;N;.;N
REVEL	Benign	0.082
Sift	Benign	1.0	.;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.017	.;B;.;.
Vest4		0.32
MutPred		0.19		.;.;Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.51
MPC		0.098
ClinPred		0.26	T
GERP RS		4.2
gMVP		0.043

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: rs1233380601; hg19: chrX-32486809;