17-9772896-C-T

Variant summary

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

The NM_001105571.3(DHRS7C):​c.598G>A​(p.Gly200Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,842 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

DHRS7C
NM_001105571.3 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.24
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 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 rank MANE Protein UniProt
DHRS7CNM_001105571.3 linkc.598G>A p.Gly200Ser missense_variant Exon 5 of 6 ENST00000571134.2 NP_001099041.1 A6NNS2-2
DHRS7CNM_001220493.2 linkc.601G>A p.Gly201Ser 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.598G>A p.Gly200Ser missense_variant Exon 5 of 6 1 NM_001105571.3 ENSP00000459579.1 A6NNS2-2
DHRS7CENST00000330255.9 linkc.601G>A p.Gly201Ser missense_variant Exon 5 of 6 1 ENSP00000327975.4 A6NNS2-1
DHRS7CENST00000571771.5 linkc.191-1200G>A intron_variant Intron 2 of 2 3 ENSP00000461902.2 I3NI52
ENSG00000282882ENST00000634974.2 linkn.146+8565C>T intron_variant Intron 1 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000360
AC:
9
AN:
249698
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135156
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461608
Hom.:
1
Cov.:
31
AF XY:
0.0000440
AC XY:
32
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000533
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152234
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000577
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 09, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.601G>A (p.G201S) 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 601, causing the glycine (G) at amino acid position 201 to be replaced by a serine (S). 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
Uncertain
0.40
BayesDel_addAF
Benign
-0.0095
T
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.092
T;.
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Uncertain
0.088
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Uncertain
0.60
D
MutationAssessor
Benign
1.3
L;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
0.050
N;.
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0090
D;.
Sift4G
Uncertain
0.017
D;D
Polyphen
1.0
D;.
Vest4
0.68
MutPred
0.75
Loss of methylation at K196 (P = 0.1275);.;
MVP
0.82
MPC
0.79
ClinPred
0.51
D
GERP RS
5.0
Varity_R
0.58
gMVP
0.92

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: rs548124003; hg19: chr17-9676213; API