14-60152940-C-T

Position:

chr14-60152940-C-T

Variant summary

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

The NM_016029.4(DHRS7):c.632G>A(p.Arg211Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R211W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

DHRS7
NM_016029.4 missense, splice_region

Scores

Splicing: ADA: 0.00004439

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

DHRS7 (HGNC:21524): (dehydrogenase/reductase 7) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family, which has over 46,000 members. Members in this family are enzymes that metabolize many different compounds, such as steroid hormones, prostaglandins, retinoids, lipids and xenobiotics. [provided by RefSeq, Apr 2016]

DHRS7 links:

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCNX4 links:

Genome browser will be placed here

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=0.14515668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DHRS7	NM_016029.4 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant, splice_region_variant	4/7	ENST00000557185.6
DHRS7	NM_001322280.2 linkuse as main transcript	c.482G>A	p.Arg161Gln	missense_variant, splice_region_variant	4/7
DHRS7	NM_001322281.2 linkuse as main transcript	c.212G>A	p.Arg71Gln	missense_variant, splice_region_variant	4/7
DHRS7	NM_001322282.2 linkuse as main transcript	c.393+1019G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHRS7	ENST00000557185.6 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant, splice_region_variant	4/7	1	NM_016029.4	P1	Q9Y394-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250332

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135392

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000683

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.632G>A (p.R211Q) alteration is located in exon 4 (coding exon 4) of the DHRS7 gene. This alteration results from a G to A substitution at nucleotide position 632, causing the arginine (R) at amino acid position 211 to be replaced by a glutamine (Q). 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

Benign

0.12

BayesDel_addAF

Benign

-0.0087

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.19

T;T;T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.90

.;D;.;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.1

L;L;.;.

MutationTaster

Benign

0.94

D;D;D;D

PrimateAI

Benign

0.24

PROVEAN

Benign

0.30

N;N;.;N

REVEL

Uncertain

0.30

Sift

Benign

0.73

T;T;.;T

Sift4G

Benign

0.72

T;T;T;T

Polyphen

0.050

B;B;.;.

Vest4

0.10

MVP

0.86

MPC

0.049

ClinPred

0.13

GERP RS

-0.40

Varity_R

0.029

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over