17-9772877-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001105571.3(DHRS7C):​c.617G>A​(p.Arg206Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DHRS7C
NM_001105571.3 missense

Scores

11
6
2

Clinical Significance

Not reported in ClinVar

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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DHRS7CNM_001105571.3 linkc.617G>A p.Arg206Gln missense_variant Exon 5 of 6 ENST00000571134.2 NP_001099041.1 A6NNS2-2
DHRS7CNM_001220493.2 linkc.620G>A p.Arg207Gln 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.617G>A p.Arg206Gln missense_variant Exon 5 of 6 1 NM_001105571.3 ENSP00000459579.1 A6NNS2-2
DHRS7CENST00000330255.9 linkc.620G>A p.Arg207Gln missense_variant Exon 5 of 6 1 ENSP00000327975.4 A6NNS2-1
DHRS7CENST00000571771.5 linkc.191-1181G>A intron_variant Intron 2 of 2 3 ENSP00000461902.2 I3NI52
ENSG00000282882ENST00000634974.2 linkn.146+8546C>T intron_variant Intron 1 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461656
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727108
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000330
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.44
T;.
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.94
D;D
MetaSVM
Pathogenic
0.91
D
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.8
D;.
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;.
Vest4
0.94
MVP
0.83
MPC
0.88
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.92
gMVP
0.93

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: rs559179095; hg19: chr17-9676194; COSMIC: COSV100364966; API