Genetic Variant DHRS7C:p.Asp213Asn (chr17-9772857-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105571.3(DHRS7C):c.637G>A(p.Asp213Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000942 in 1,613,940 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 1 hom. )

Consequence

DHRS7C
NM_001105571.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

Variant links:

Genes affected

DHRS7C (HGNC:32423): (dehydrogenase/reductase 7C) Predicted to enable NAD-retinol dehydrogenase activity. Predicted to be involved in regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum. Predicted to be located in extracellular region and longitudinal sarcoplasmic reticulum. Predicted to be active in sarcoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

DHRS7C links:

ENSG00000282882 (HGNC:):

ENSG00000282882 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03813964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7C	NM_001105571.3 link	c.637G>A	p.Asp213Asn	missense_variant	Exon 5 of 6	ENST00000571134.2	NP_001099041.1	A6NNS2-2
DHRS7C	NM_001220493.2 link	c.640G>A	p.Asp214Asn	missense_variant	Exon 5 of 6		NP_001207422.1	A6NNS2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHRS7C	ENST00000571134.2 link	c.637G>A	p.Asp213Asn	missense_variant	Exon 5 of 6	1	NM_001105571.3	ENSP00000459579.1	A6NNS2-2
DHRS7C	ENST00000330255.9 link	c.640G>A	p.Asp214Asn	missense_variant	Exon 5 of 6	1		ENSP00000327975.4	A6NNS2-1
DHRS7C	ENST00000571771.5 link	c.191-1161G>A		intron_variant	Intron 2 of 2	3		ENSP00000461902.2	I3NI52
ENSG00000282882	ENST00000634974.2 link	n.146+8526C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000680

AC:

AN:

249826

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000575

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000447

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00157

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000121

Hom.:

Bravo

AF:

0.000453

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.640G>A (p.D214N) alteration is located in exon 5 (coding exon 5) of the DHRS7C gene. This alteration results from a G to A substitution at nucleotide position 640, causing the aspartic acid (D) at amino acid position 214 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

M;.

PrimateAI

Benign

0.39

PROVEAN

Benign

0.74

N;.

REVEL

Benign

0.086

Sift

Benign

0.80

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.80

P;.

Vest4

0.31

MVP

0.31

MPC

0.25

ClinPred

0.074

GERP RS

4.0

Varity_R

0.094

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over