Genetic Variant SDR39U1:p.Gly108Val (chr14-24441679-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387324.1(SDR39U1):c.322+1G>T variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,431,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SDR39U1
NM_001387324.1 splice_donor, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.38

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387324.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDR39U1	NM_020195.3	MANE Select	c.323G>T	p.Gly108Val	missense	Exon 4 of 6	NP_064580.2	Q9NRG7-2
KHNYN	NM_015299.3	MANE Select	c.*4394C>A		3_prime_UTR	Exon 8 of 8	NP_056114.1	O15037
SDR39U1	NM_001387322.1		c.392G>T	p.Gly131Val	missense	Exon 4 of 6	NP_001374251.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDR39U1	ENST00000399395.8	TSL:1 MANE Select	c.323G>T	p.Gly108Val	missense	Exon 4 of 6	ENSP00000382327.3	Q9NRG7-2
KHNYN	ENST00000553935.6	TSL:1 MANE Select	c.*4394C>A		3_prime_UTR	Exon 8 of 8	ENSP00000450799.1	O15037
KHNYN	ENST00000251343.9	TSL:1	c.*4394C>A		3_prime_UTR	Exon 8 of 8	ENSP00000251343.5	O15037

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1431410

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31330

American (AMR)

AF:

0.00

AC:

AN:

33528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24642

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

81286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1103408

Other (OTH)

AF:

0.00

AC:

AN:

59066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.95

MetaSVM

Pathogenic

0.88

PhyloP100

7.4

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.9

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.92

MVP

0.67

MPC

0.49

ClinPred

1.0

GERP RS

5.5

gMVP

0.93

Mutation Taster

=173/127

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over