chr17-9777222-C-T

Variant names:

• chr17-9777222-C-T
• NM_001105571.3:c.542G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001105571.3(DHRS7C):​c.542G>A​(p.Gly181Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.59

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7C	NM_001105571.3	c.542G>A	p.Gly181Glu	missense_variant	Exon 4 of 6	ENST00000571134.2	NP_001099041.1
DHRS7C	NM_001220493.2	c.545G>A	p.Gly182Glu	missense_variant	Exon 4 of 6		NP_001207422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS7C	ENST00000571134.2	c.542G>A	p.Gly181Glu	missense_variant	Exon 4 of 6	1	NM_001105571.3	ENSP00000459579.1
DHRS7C	ENST00000330255.9	c.545G>A	p.Gly182Glu	missense_variant	Exon 4 of 6	1		ENSP00000327975.4
DHRS7C	ENST00000571771.5	c.161G>A	p.Gly54Glu	missense_variant	Exon 2 of 3	3		ENSP00000461902.2
ENSG00000282882	ENST00000634974.2	n.147-5697C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.545G>A (p.G182E) alteration is located in exon 4 (coding exon 4) of the DHRS7C gene. This alteration results from a G to A substitution at nucleotide position 545, causing the glycine (G) at amino acid position 182 to be replaced by a glutamic acid (E). 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	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Benign	0.81
DEOGEN2	Uncertain	0.61	.;D;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	3.3	.;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-7.3	.;D;.
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	.;D;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.79, 0.80
MutPred		0.98		.;Gain of ubiquitination at K183 (P = 0.0528);.;
MVP		0.67
MPC		0.92
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.98
gMVP		0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-9680539;