17-9771526-C-G

Variant names:

• chr17-9771526-C-G
• rs753331851
• NM_001105571.3:c.898G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001105571.3(DHRS7C):​c.898G>C​(p.Gly300Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000887 in 1,577,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: DHRS7C NM_001105571.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.898G>C	p.Gly300Arg	missense	Exon 6 of 6	NP_001099041.1	A6NNS2-2
	DHRS7C	NM_001220493.2		c.901G>C	p.Gly301Arg	missense	Exon 6 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.898G>C	p.Gly300Arg	missense	Exon 6 of 6	ENSP00000459579.1	A6NNS2-2
	DHRS7C	ENST00000330255.9	TSL:1	c.901G>C	p.Gly301Arg	missense	Exon 6 of 6	ENSP00000327975.4	A6NNS2-1
	DHRS7C	ENST00000571771.5	TSL:3	c.361G>C	p.Gly121Arg	missense	Exon 3 of 3	ENSP00000461902.2	I3NI52

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000444 AC: 1 AN: 225068 AF XY: 0.00000821

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000970

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000912 AC: 13 AN: 1425464 Hom.: 0 Cov.: 30 AF XY: 0.00000708 AC XY: 5 AN XY: 705944

African (AFR) AF: 0.00 AC: 0 AN: 32380

American (AMR) AF: 0.00 AC: 0 AN: 41266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24714

East Asian (EAS) AF: 0.00 AC: 0 AN: 37840

South Asian (SAS) AF: 0.00 AC: 0 AN: 81288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52654

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5624

European-Non Finnish (NFE) AF: 0.00000917 AC: 10 AN: 1090924

Other (OTH) AF: 0.0000340 AC: 2 AN: 58774

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

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	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	2.2	N
REVEL	Uncertain	0.59
Sift	Benign	0.94	T
Sift4G	Benign	0.83	T
Polyphen		0.99	D
Vest4		0.92
MutPred		0.52		Gain of methylation at G301 (P = 0.038)
MVP		0.82
MPC		0.82
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.81
Mutation Taster		=41/59	disease causing

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: rs753331851; hg19: chr17-9674843;