rs1060502614

Variant names:

• chrX-31929669-C-A
• NM_004006.3:c.6839G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-31929669-C-A
• chrX-31929669-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004021.3(DMD):​c.-542G>T variant causes a 5 prime UTR premature start codon gain 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: DMD NM_004021.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.6839G>T	p.Ser2280Ile	missense_variant	Exon 47 of 79	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.6839G>T	p.Ser2280Ile	missense_variant	Exon 47 of 79	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	0.0030	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	.;T;.;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T;.;T;T
M_CAP	Pathogenic	0.81	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-0.66	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	.;N;.;N
REVEL	Benign	0.19
Sift	Uncertain	0.018	.;D;.;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		1.0	.;D;.;.
Vest4		0.68
MutPred		0.54		.;.;.;Loss of disorder (P = 0.0055);
MVP		0.67
MPC		0.056
ClinPred		0.85	D
GERP RS		5.0
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-31947786;