chr17-9772857-C-T

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

1
18

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]

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
DHRS7CNM_001105571.3 linkc.637G>A p.Asp213Asn missense_variant Exon 5 of 6 ENST00000571134.2 NP_001099041.1 A6NNS2-2
DHRS7CNM_001220493.2 linkc.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 Appris UniProt
DHRS7CENST00000571134.2 linkc.637G>A p.Asp213Asn missense_variant Exon 5 of 6 1 NM_001105571.3 ENSP00000459579.1 A6NNS2-2
DHRS7CENST00000330255.9 linkc.640G>A p.Asp214Asn missense_variant Exon 5 of 6 1 ENSP00000327975.4 A6NNS2-1
DHRS7CENST00000571771.5 linkc.191-1161G>A intron_variant Intron 2 of 2 3 ENSP00000461902.2 I3NI52
ENSG00000282882ENST00000634974.2 linkn.146+8526C>T intron_variant Intron 1 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.000434
AC:
66
AN:
152132
Hom.:
0
Cov.:
32
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:
17
AN:
249826
Hom.:
0
AF XY:
0.0000296
AC XY:
4
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:
84
AN:
1461690
Hom.:
1
Cov.:
31
AF XY:
0.0000399
AC XY:
29
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:
68
AN:
152250
Hom.:
0
Cov.:
32
AF XY:
0.000417
AC XY:
31
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.:
0
Bravo
AF:
0.000453
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000577
AC:
2
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
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
17
DANN
Benign
0.62
DEOGEN2
Benign
0.061
T;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.21
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.9
M;.
PrimateAI
Benign
0.39
T
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
T
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.

Other links and lift over

dbSNP: rs201098406; hg19: chr17-9676174; COSMIC: COSV57653031; API