14-24440438-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020195.3(SDR39U1):​c.527G>A​(p.Arg176His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,611,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R176C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SDR39U1
NM_020195.3 missense

Scores

4
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39072883).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDR39U1NM_020195.3 linkc.527G>A p.Arg176His missense_variant Exon 6 of 6 ENST00000399395.8 NP_064580.2 Q9NRG7-2Q86TZ5
KHNYNNM_015299.3 linkc.*3153C>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.527G>A p.Arg176His missense_variant Exon 6 of 6 1 NM_020195.3 ENSP00000382327.3 Q9NRG7-2
KHNYNENST00000553935.6 linkc.*3153C>T 3_prime_UTR_variant Exon 8 of 8 1 NM_015299.3 ENSP00000450799.1 O15037

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152170
Hom.:
0
Cov.:
33
show subpopulations
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:
0.000118
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000419
AC:
10
AN:
238900
Hom.:
0
AF XY:
0.0000537
AC XY:
7
AN XY:
130394
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:
0.0000333
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000846
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000106
AC:
155
AN:
1459694
Hom.:
0
Cov.:
48
AF XY:
0.000114
AC XY:
83
AN XY:
725936
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.000129
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152170
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000118
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000901
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000121
AC:
1
ExAC
AF:
0.0000331
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.527G>A (p.R176H) 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 527, causing the arginine (R) at amino acid position 176 to be replaced by a histidine (H). 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
-0.16
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.065
.;T;T;.;T;T;.;.;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.39
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.13
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.17
Sift
Benign
0.38
T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.56
T;T;T;T;T;.;.;.;.
Polyphen
1.0
D;D;D;D;.;.;.;.;.
Vest4
0.39
MVP
0.45
MPC
0.37
ClinPred
0.94
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.56

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: rs373631253; hg19: chr14-24909644; COSMIC: COSV99063444; COSMIC: COSV99063444; API