chr17-9780032-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001105571.3(DHRS7C):​c.271T>C​(p.Phe91Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DHRS7C
NM_001105571.3 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.76
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3975454).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DHRS7CNM_001105571.3 linkc.271T>C p.Phe91Leu missense_variant Exon 3 of 6 ENST00000571134.2 NP_001099041.1 A6NNS2-2
DHRS7CNM_001220493.2 linkc.274T>C p.Phe92Leu missense_variant Exon 3 of 6 NP_001207422.1 A6NNS2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DHRS7CENST00000571134.2 linkc.271T>C p.Phe91Leu missense_variant Exon 3 of 6 1 NM_001105571.3 ENSP00000459579.1 A6NNS2-2
DHRS7CENST00000330255.9 linkc.274T>C p.Phe92Leu missense_variant Exon 3 of 6 1 ENSP00000327975.4 A6NNS2-1
ENSG00000282882ENST00000634974.2 linkn.147-2887A>G intron_variant Intron 1 of 3 5
DHRS7CENST00000571771.5 linkc.-111T>C upstream_gene_variant 3 ENSP00000461902.2 I3NI52

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461206
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726804
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 10, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.274T>C (p.F92L) alteration is located in exon 3 (coding exon 3) of the DHRS7C gene. This alteration results from a T to C substitution at nucleotide position 274, causing the phenylalanine (F) at amino acid position 92 to be replaced by a leucine (L). 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
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.40
T;T
MetaSVM
Uncertain
0.0016
D
MutationAssessor
Benign
0.30
N;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.2
D;.
REVEL
Pathogenic
0.70
Sift
Benign
0.15
T;.
Sift4G
Benign
0.27
T;T
Polyphen
0.96
D;.
Vest4
0.44
MutPred
0.40
Gain of ubiquitination at K89 (P = 0.0804);.;
MVP
0.77
MPC
0.82
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.38
gMVP
0.75

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: rs2066384875; hg19: chr17-9683349; API