chr17-9780032-A-G

Variant names:

• chr17-9780032-A-G
• rs2066384875
• NM_001105571.3:c.271T>C

Variant summary

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

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.76

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=0.3975454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7C	NM_001105571.3	c.271T>C	p.Phe91Leu	missense_variant	Exon 3 of 6	ENST00000571134.2	NP_001099041.1
DHRS7C	NM_001220493.2	c.274T>C	p.Phe92Leu	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.271T>C	p.Phe91Leu	missense_variant	Exon 3 of 6	1	NM_001105571.3	ENSP00000459579.1
DHRS7C	ENST00000330255.9	c.274T>C	p.Phe92Leu	missense_variant	Exon 3 of 6	1		ENSP00000327975.4
ENSG00000282882	ENST00000634974.2	n.147-2887A>G		intron_variant	Intron 1 of 3	5
DHRS7C	ENST00000571771.5	c.-111T>C		upstream_gene_variant		3		ENSP00000461902.2

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

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

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

Other links and lift over

dbSNP: rs2066384875; hg19: chr17-9683349;