14-24440249-C-T

Variant summary

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

The NM_020195.3(SDR39U1):​c.716G>A​(p.Arg239Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SDR39U1
NM_020195.3 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99
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]
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]

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=0.16025615).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDR39U1NM_020195.3 linkc.716G>A p.Arg239Gln missense_variant Exon 6 of 6 ENST00000399395.8 NP_064580.2 Q9NRG7-2Q86TZ5
KHNYNNM_015299.3 linkc.*2964C>T 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
SDR39U1ENST00000399395.8 linkc.716G>A p.Arg239Gln missense_variant Exon 6 of 6 1 NM_020195.3 ENSP00000382327.3 Q9NRG7-2
KHNYNENST00000553935.6 linkc.*2964C>T 3_prime_UTR_variant Exon 8 of 8 1 NM_015299.3 ENSP00000450799.1 O15037

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152212
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000145
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000406
AC:
10
AN:
246476
Hom.:
0
AF XY:
0.0000299
AC XY:
4
AN XY:
133956
show subpopulations
Gnomad AFR exome
AF:
0.000194
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000272
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461542
Hom.:
0
Cov.:
68
AF XY:
0.0000220
AC XY:
16
AN XY:
727030
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152212
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000137
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.716G>A (p.R239Q) alteration is located in exon 6 (coding exon 6) of the SDR39U1 gene. This alteration results from a G to A substitution at nucleotide position 716, causing the arginine (R) at amino acid position 239 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
-0.34
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
.;T;T;.;T;T;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.083
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.95
D;D;D;D;D;D;D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.16
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.90
N;N;N;N;N;N;N;N
REVEL
Benign
0.16
Sift
Uncertain
0.0050
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D;.;.;.
Polyphen
0.37
B;D;P;B;.;.;.;.
Vest4
0.18
MVP
0.17
MPC
0.11
ClinPred
0.11
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs765594883; hg19: chr14-24909455; API