chr17-9780032-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3975454).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105571.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS7C	NM_001105571.3	MANE Select	c.271T>C	p.Phe91Leu	missense	Exon 3 of 6	NP_001099041.1	A6NNS2-2
	DHRS7C	NM_001220493.2		c.274T>C	p.Phe92Leu	missense	Exon 3 of 6	NP_001207422.1	A6NNS2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS7C	ENST00000571134.2	TSL:1 MANE Select	c.271T>C	p.Phe91Leu	missense	Exon 3 of 6	ENSP00000459579.1	A6NNS2-2
	DHRS7C	ENST00000330255.9	TSL:1	c.274T>C	p.Phe92Leu	missense	Exon 3 of 6	ENSP00000327975.4	A6NNS2-1
	ENSG00000282882	ENST00000634974.2	TSL:5	n.147-2887A>G		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111746

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.0016	D
MutationAssessor	Benign	0.30	N
PhyloP100		8.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.2	D
REVEL	Pathogenic	0.70
Sift	Benign	0.15	T
Sift4G	Benign	0.27	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
PromoterAI		-0.047	Neutral
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

Other links and lift over

dbSNP: rs2066384875; hg19: chr17-9683349;