17-9772877-C-T

Variant names:

• chr17-9772877-C-T
• rs559179095
• NM_001105571.3:c.617G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.24

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 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
DHRS7C	NM_001105571.3	c.617G>A	p.Arg206Gln	missense_variant	Exon 5 of 6	ENST00000571134.2	NP_001099041.1
DHRS7C	NM_001220493.2	c.620G>A	p.Arg207Gln	missense_variant	Exon 5 of 6		NP_001207422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS7C	ENST00000571134.2	c.617G>A	p.Arg206Gln	missense_variant	Exon 5 of 6	1	NM_001105571.3	ENSP00000459579.1
DHRS7C	ENST00000330255.9	c.620G>A	p.Arg207Gln	missense_variant	Exon 5 of 6	1		ENSP00000327975.4
DHRS7C	ENST00000571771.5	c.191-1181G>A		intron_variant	Intron 2 of 2	3		ENSP00000461902.2
ENSG00000282882	ENST00000634974.2	n.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

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

Other links and lift over

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