17-9779876-C-G

Variant names:

• chr17-9779876-C-G
• NM_001105571.3:c.427G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001105571.3(DHRS7C):​c.427G>C​(p.Asp143His) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 7.42

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7C	NM_001105571.3	c.427G>C	p.Asp143His	missense_variant	Exon 3 of 6	ENST00000571134.2	NP_001099041.1
DHRS7C	NM_001220493.2	c.430G>C	p.Asp144His	missense_variant	Exon 3 of 6		NP_001207422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS7C	ENST00000571134.2	c.427G>C	p.Asp143His	missense_variant	Exon 3 of 6	1	NM_001105571.3	ENSP00000459579.1
DHRS7C	ENST00000330255.9	c.430G>C	p.Asp144His	missense_variant	Exon 3 of 6	1		ENSP00000327975.4
DHRS7C	ENST00000571771.5	c.46G>C	p.Asp16His	missense_variant	Exon 1 of 3	3		ENSP00000461902.2
ENSG00000282882	ENST00000634974.2	n.147-3043C>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.430G>C (p.D144H) alteration is located in exon 3 (coding exon 3) of the DHRS7C gene. This alteration results from a G to C substitution at nucleotide position 430, causing the aspartic acid (D) at amino acid position 144 to be replaced by a histidine (H). 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	0.85
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;T;.
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	-0.20	.;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.3	.;D;.
REVEL	Pathogenic	0.79
Sift	Benign	0.036	.;D;.
Sift4G	Benign	0.076	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.90, 0.91
MutPred		0.58		.;Gain of methylation at K145 (P = 0.0765);.;
MVP		0.75
MPC		0.89
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.76
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr17-9683193;