14-24440205-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020195.3(SDR39U1):​c.760G>A​(p.Gly254Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SDR39U1
NM_020195.3 missense

Scores

10
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.20
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDR39U1NM_020195.3 linkc.760G>A p.Gly254Arg missense_variant Exon 6 of 6 ENST00000399395.8 NP_064580.2 Q9NRG7-2Q86TZ5
KHNYNNM_015299.3 linkc.*2920C>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.760G>A p.Gly254Arg missense_variant Exon 6 of 6 1 NM_020195.3 ENSP00000382327.3 Q9NRG7-2
KHNYNENST00000553935.6 linkc.*2920C>T 3_prime_UTR_variant Exon 8 of 8 1 NM_015299.3 ENSP00000450799.1 O15037

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461608
Hom.:
0
Cov.:
68
AF XY:
0.00
AC XY:
0
AN XY:
727078
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.760G>A (p.G254R) 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 760, causing the glycine (G) at amino acid position 254 to be replaced by an arginine (R). 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
Pathogenic
0.70
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.33
.;T;T;.;T;T;.
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D;D;D;D;D
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.88
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.27
D
PrimateAI
Uncertain
0.63
T
PROVEAN
Pathogenic
-5.7
D;D;D;D;D;D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0020
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D;.;.
Polyphen
1.0
D;D;D;D;.;.;.
Vest4
0.95
MVP
0.64
MPC
0.49
ClinPred
1.0
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24909411; API