chr19-45786179-C-T

Variant names:

• chr19-45786179-C-T
• rs759194755
• NM_004943.2:c.1317G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004943.2(DMWD):​c.1317G>A​(p.Gln439Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,450,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DMWD NM_004943.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 0 publications found

Genes affected

DMWD (HGNC:2936): (DM1 locus, WD repeat containing) Predicted to be located in dendrite; nucleus; and perikaryon. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268434 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=3.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMWD	NM_004943.2	c.1317G>A	p.Gln439Gln	synonymous_variant	Exon 3 of 5	ENST00000270223.7	NP_004934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMWD	ENST00000270223.7	c.1317G>A	p.Gln439Gln	synonymous_variant	Exon 3 of 5	1	NM_004943.2	ENSP00000270223.5
DMWD	ENST00000377735.7	c.1317G>A	p.Gln439Gln	synonymous_variant	Exon 3 of 4	5		ENSP00000366964.3
ENSG00000268434	ENST00000593999.1	n.-208G>A		upstream_gene_variant		2		ENSP00000471312.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000446 AC: 1 AN: 224106 AF XY: 0.00000810

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 AF: 0.00000414 AC: 6 AN: 1450048 Hom.: 0 Cov.: 71 AF XY: 0.00000555 AC XY: 4 AN XY: 720638

African (AFR) AF: 0.0000301 AC: 1 AN: 33244

American (AMR) AF: 0.00 AC: 0 AN: 43194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25616

East Asian (EAS) AF: 0.00 AC: 0 AN: 39168

South Asian (SAS) AF: 0.0000353 AC: 3 AN: 84874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107118

Other (OTH) AF: 0.00 AC: 0 AN: 59778

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.0
DANN	Benign	0.76
PhyloP100		3.2
PromoterAI		-0.00080	Neutral

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: rs759194755; hg19: chr19-46289437; COSMIC: COSV99352753; COSMIC: COSV99352753;