rs62620995

Variant names:

• chr8-104355036-C-T
• rs62620995
• NM_030788.4:c.1189C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_030788.4(DCSTAMP):​c.1189C>T​(p.Leu397Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,074 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.0091 (13 hom., cov: 32)
  • Exomes 𝑓: 0.012 (142 hom.)
• Consequence: DCSTAMP NM_030788.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 13 publications found

Genes affected

DCSTAMP (HGNC:18549): (dendrocyte expressed seven transmembrane protein) This gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells. The encoded protein is involved in a range of immunological functions carried out by dendritic cells. This protein plays a role in osteoclastogenesis and myeloid differentiation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

DPYS (HGNC:3013): (dihydropyrimidinase) Dihydropyrimidinase catalyzes the conversion of 5,6-dihydrouracil to 3-ureidopropionate in pyrimidine metabolism. Dihydropyrimidinase is expressed at a high level in liver and kidney as a major 2.5-kb transcript and a minor 3.8-kb transcript. Defects in the DPYS gene are linked to dihydropyrimidinuria. [provided by RefSeq, Jul 2008]

DPYS Gene-Disease associations (from GenCC):

• dihydropyrimidinuria

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007275045).
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030788.4. 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
	DCSTAMP	NM_030788.4	MANE Select	c.1189C>T	p.Leu397Phe	missense	Exon 3 of 4	NP_110415.1	Q9H295-1
	DCSTAMP	NM_001257317.1		c.828-1088C>T		intron	N/A	NP_001244246.1	Q9H295-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCSTAMP	ENST00000297581.2	TSL:1 MANE Select	c.1189C>T	p.Leu397Phe	missense	Exon 3 of 4	ENSP00000297581.2	Q9H295-1
	DCSTAMP	ENST00000517991.5	TSL:1	c.828-1088C>T		intron	N/A	ENSP00000428869.1	Q9H295-2
	DPYS	ENST00000908793.1		c.*15-7829G>A		intron	N/A	ENSP00000578852.1

Frequencies

GnomAD3 genomes AF: 0.00914 AC: 1391 AN: 152116 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00911

GnomAD2 exomes AF: 0.00867 AC: 2180 AN: 251382 AF XY: 0.00875

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00892

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.00913

GnomAD4 exome AF: 0.0121 AC: 17704 AN: 1461840 Hom.: 142 Cov.: 32 AF XY: 0.0119 AC XY: 8638 AN XY: 727228

African (AFR) AF: 0.00215 AC: 72 AN: 33478

American (AMR) AF: 0.00510 AC: 228 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26136

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39698

South Asian (SAS) AF: 0.00576 AC: 497 AN: 86256

European-Finnish (FIN) AF: 0.00996 AC: 532 AN: 53418

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0142 AC: 15741 AN: 1111968

Other (OTH) AF: 0.00969 AC: 585 AN: 60394

GnomAD4 genome AF: 0.00914 AC: 1391 AN: 152234 Hom.: 13 Cov.: 32 AF XY: 0.00930 AC XY: 692 AN XY: 74414

African (AFR) AF: 0.00272 AC: 113 AN: 41532

American (AMR) AF: 0.00837 AC: 128 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4822

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0145 AC: 986 AN: 68012

Other (OTH) AF: 0.00901 AC: 19 AN: 2108

Alfa AF: 0.0123 Hom.: 50

Bravo AF: 0.00822

TwinsUK AF: 0.0167 AC: 62

ALSPAC AF: 0.0179 AC: 69

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0124 AC: 107

ExAC AF: 0.00921 AC: 1118

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0118

EpiControl AF: 0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.65
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.16
Sift	Benign	0.088	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.46
MVP		0.53
MPC		0.33
ClinPred		0.024	T
GERP RS		5.4
Varity_R		0.18
gMVP		0.72
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs62620995; hg19: chr8-105367264;