NM_177986.5:c.30C>T

Variant names:

• chr18-31376941-C-T
• rs36101975
• NM_177986.5:c.30C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_177986.5(DSG4):​c.30C>T​(p.Cys10Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,612,720 control chromosomes in the GnomAD database, including 16,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1471 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15091 hom.)
• Consequence: DSG4 NM_177986.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.126
• Publications: 14 publications found

Genes affected

DSG4 (HGNC:21307): (desmoglein 4) This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth. [provided by RefSeq, May 2016]

DSG1-AS1 (HGNC:51115): (DSG1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 18-31376941-C-T is Benign according to our data. Variant chr18-31376941-C-T is described in ClinVar as Benign. ClinVar VariationId is 326416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.126 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177986.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG4	NM_177986.5	MANE Select	c.30C>T	p.Cys10Cys	synonymous	Exon 1 of 16	NP_817123.1	Q86SJ6-1
	DSG4	NM_001134453.3		c.30C>T	p.Cys10Cys	synonymous	Exon 1 of 15	NP_001127925.1	Q86SJ6-2
	DSG1-AS1	NR_110788.1		n.157-22488G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG4	ENST00000308128.9	TSL:1 MANE Select	c.30C>T	p.Cys10Cys	synonymous	Exon 1 of 16	ENSP00000311859.4	Q86SJ6-1
	DSG4	ENST00000359747.4	TSL:1	c.30C>T	p.Cys10Cys	synonymous	Exon 1 of 15	ENSP00000352785.4	Q86SJ6-2
	DSG1-AS1	ENST00000578477.6	TSL:3	n.157-12656G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21154 AN: 151968 Hom.: 1472 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.138

GnomAD2 exomes AF: 0.138 AC: 34485 AN: 250536 AF XY: 0.143

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0696

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.121

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.142 AC: 207172 AN: 1460630 Hom.: 15091 Cov.: 31 AF XY: 0.142 AC XY: 103389 AN XY: 726638

African (AFR) AF: 0.135 AC: 4501 AN: 33436

American (AMR) AF: 0.0725 AC: 3235 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4833 AN: 26108

East Asian (EAS) AF: 0.120 AC: 4748 AN: 39644

South Asian (SAS) AF: 0.161 AC: 13886 AN: 86214

European-Finnish (FIN) AF: 0.137 AC: 7295 AN: 53374

Middle Eastern (MID) AF: 0.206 AC: 1186 AN: 5762

European-Non Finnish (NFE) AF: 0.143 AC: 159174 AN: 1111116

Other (OTH) AF: 0.138 AC: 8314 AN: 60330

GnomAD4 genome AF: 0.139 AC: 21166 AN: 152090 Hom.: 1471 Cov.: 32 AF XY: 0.138 AC XY: 10260 AN XY: 74352

African (AFR) AF: 0.135 AC: 5594 AN: 41502

American (AMR) AF: 0.101 AC: 1539 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3466

East Asian (EAS) AF: 0.113 AC: 585 AN: 5176

South Asian (SAS) AF: 0.157 AC: 758 AN: 4814

European-Finnish (FIN) AF: 0.128 AC: 1357 AN: 10564

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10110 AN: 67982

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.147 Hom.: 5369

Bravo AF: 0.134

Asia WGS AF: 0.105 AC: 365 AN: 3478

EpiCase AF: 0.150

EpiControl AF: 0.153

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hypotrichosis 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.1
DANN	Benign	0.57
PhyloP100		0.13
PromoterAI		-0.0056	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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: rs36101975; hg19: chr18-28956904; COSMIC: COSV57389432;