rs375422080

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020195.3(SDR39U1):c.739G>T(p.Ala247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

SDR39U1
NM_020195.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.566

Variant links:

Genes affected

SDR39U1 (HGNC:20275): (short chain dehydrogenase/reductase family 39U member 1) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) superfamily, which includes both classical and extended types. The encoded protein represents an extended type, with similarity to epimerases. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Mar 2014]

SDR39U1 links:

KHNYN (HGNC:20166): (KH and NYN domain containing) The protein encoded by this gene contains a ribonuclease NYN domain and belongs to the N4BP1 family. The protein is a cofactor for the zinc finger antiviral protein (ZAP protein) which targets viral RNA for degradation and restricts SARS-CoV-2 infection. [provided by RefSeq, Sep 2021]

KHNYN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019552797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDR39U1	NM_020195.3 link	c.739G>T	p.Ala247Ser	missense_variant	Exon 6 of 6	ENST00000399395.8	NP_064580.2	Q9NRG7-2Q86TZ5
KHNYN	NM_015299.3 link	c.*2941C>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000553935.6	NP_056114.1	O15037

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDR39U1	ENST00000399395.8 link	c.739G>T	p.Ala247Ser	missense_variant	Exon 6 of 6	1	NM_020195.3	ENSP00000382327.3		Q9NRG7-2
KHNYN	ENST00000553935.6 link	c.*2941C>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_015299.3	ENSP00000450799.1		O15037

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000730

AC:

AN:

246558

Hom.:

AF XY:

0.0000672

AC XY:

AN XY:

134010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000634

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000744

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.739G>T (p.A247S) alteration is located in exon 6 (coding exon 6) of the SDR39U1 gene. This alteration results from a G to T substitution at nucleotide position 739, causing the alanine (A) at amino acid position 247 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.31

DANN

Benign

0.90

DEOGEN2

Benign

0.0098

.;T;T;.;T;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.076

T;T;T;T;T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.020

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.21

N;N;N;N;N;N;N;N

REVEL

Benign

0.013

Sift

Uncertain

0.018

D;T;D;D;D;D;T;T

Sift4G

Benign

0.085

T;T;T;T;T;.;.;.

Polyphen

0.028

B;B;B;B;.;.;.;.

Vest4

0.14

MVP

0.10

MPC

0.080

ClinPred

0.028

GERP RS

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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