dbSNP rs746479641: DHRS13:p.Arg185Leu (chr17-28901118-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144683.4(DHRS13):c.554G>T(p.Arg185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. R185H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DHRS13
NM_144683.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Variant links:

Genes affected

DHRS13 (HGNC:28326): (dehydrogenase/reductase 13) Predicted to enable NADP-retinol dehydrogenase activity. Predicted to be involved in retinal metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DHRS13 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.075787544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS13	NM_144683.4 link	c.554G>T	p.Arg185Leu	missense_variant	Exon 4 of 5	ENST00000378895.9	NP_653284.2	Q6UX07-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHRS13	ENST00000378895.9 link	c.554G>T	p.Arg185Leu	missense_variant	Exon 4 of 5	1	NM_144683.4	ENSP00000368173.4	Q6UX07-1
DHRS13	ENST00000394901.7 link	c.404G>T	p.Arg135Leu	missense_variant	Exon 3 of 4	1		ENSP00000378361.3	Q6UX07-2
DHRS13	ENST00000581759.1 link	n.818G>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
DHRS13	ENST00000426464.2 link	c.311G>T	p.Arg104Leu	missense_variant	Exon 2 of 3	2		ENSP00000412826.2	Q6UX07-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251230

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135852

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0060

T;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.39

N;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.060

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.66

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.11

B;.;.

Vest4

0.22

MutPred

0.48

Loss of MoRF binding (P = 0.0104);.;.;

MVP

0.46

MPC

0.43

ClinPred

0.075

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.086

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over