rs397515640

Positions:

• chr18-31331784-C-A
• chr18-31331784-C-T

Variant summary

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

The NM_001942.4(DSG1):​c.601C>A​(p.Gln201Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSG1 NM_001942.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71

Genes affected

DSG1 (HGNC:3048): (desmoglein 1) This gene encodes a member of the desmoglein protein subfamily. Desmogleins, along with desmocollins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmoglein family members on chromosome 18. The encoded protein has been identified as a target of auto-antibodies in the autoimmune skin blistering disease pemphigus foliaceus. Disruption of this gene has also been associated with the skin diseases palmoplantar keratoderma and erythroderma. [provided by RefSeq, Feb 2015]

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
DSG1	NM_001942.4	c.601C>A	p.Gln201Lys	missense_variant	6/15	ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5	c.601C>A	p.Gln201Lys	missense_variant	6/15	1	NM_001942.4	ENSP00000257192	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.00032	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.56		Gain of methylation at Q201 (P = 0.0197);
MVP		0.63
MPC		0.47
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.77
gMVP		0.67

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: rs397515640; hg19: chr18-28911747;