chr17-9771553-C-G

Variant names:

• chr17-9771553-C-G
• NM_001105571.3:c.871G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001105571.3(DHRS7C):​c.871G>C​(p.Glu291Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: DHRS7C NM_001105571.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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]

ENSG00000282882 (HGNC:):

ACMG classification

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=0.2767049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7C	NM_001105571.3	c.871G>C	p.Glu291Gln	missense_variant	Exon 6 of 6	ENST00000571134.2	NP_001099041.1
DHRS7C	NM_001220493.2	c.874G>C	p.Glu292Gln	missense_variant	Exon 6 of 6		NP_001207422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS7C	ENST00000571134.2	c.871G>C	p.Glu291Gln	missense_variant	Exon 6 of 6	1	NM_001105571.3	ENSP00000459579.1
DHRS7C	ENST00000330255.9	c.874G>C	p.Glu292Gln	missense_variant	Exon 6 of 6	1		ENSP00000327975.4
DHRS7C	ENST00000571771.5	c.334G>C	p.Glu112Gln	missense_variant	Exon 3 of 3	3		ENSP00000461902.2
ENSG00000282882	ENST00000634974.2	n.146+7222C>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.874G>C (p.E292Q) alteration is located in exon 6 (coding exon 6) of the DHRS7C gene. This alteration results from a G to C substitution at nucleotide position 874, causing the glutamic acid (E) at amino acid position 292 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0063	.;T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	-0.041	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.29	.;N;.
REVEL	Benign	0.27
Sift	Benign	0.53	.;T;.
Sift4G	Benign	0.53	T;T;T
Polyphen		0.93	.;P;.
Vest4		0.16, 0.17
MutPred		0.51		.;Loss of helix (P = 0.028);.;
MVP		0.54
MPC		0.23
ClinPred		0.60	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-9674870;