rs375422080

Variant names:

• chr14-24440226-C-A
• rs375422080
• NM_020195.3:c.739G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-24440226-C-A
• chr14-24440226-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 15/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.566
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019552797).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020195.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR39U1	NM_020195.3	MANE Select	c.739G>T	p.Ala247Ser	missense	Exon 6 of 6	NP_064580.2	Q9NRG7-2
	KHNYN	NM_015299.3	MANE Select	c.*2941C>A		3_prime_UTR	Exon 8 of 8	NP_056114.1	O15037
	SDR39U1	NM_001387322.1		c.808G>T	p.Ala270Ser	missense	Exon 6 of 6	NP_001374251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR39U1	ENST00000399395.8	TSL:1 MANE Select	c.739G>T	p.Ala247Ser	missense	Exon 6 of 6	ENSP00000382327.3	Q9NRG7-2
	SDR39U1	ENST00000554698.5	TSL:1	c.415G>T	p.Ala139Ser	missense	Exon 4 of 4	ENSP00000452438.1	Q86TZ5
	KHNYN	ENST00000553935.6	TSL:1 MANE Select	c.*2941C>A		3_prime_UTR	Exon 8 of 8	ENSP00000450799.1	O15037

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152246 Hom.: 0 Cov.: 34

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

GnomAD2 exomes AF: 0.0000730 AC: 18 AN: 246558 AF XY: 0.0000672

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000634

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000643 AC: 94 AN: 1461600 Hom.: 0 Cov.: 69 AF XY: 0.0000660 AC XY: 48 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111784

Other (OTH) AF: 0.000182 AC: 11 AN: 60366

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152246 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68050

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000901 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.0000744 AC: 9

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.31
DANN	Benign	0.90
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.076	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.57
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.013
Sift	Uncertain	0.018	D
Sift4G	Benign	0.085	T
Polyphen		0.028	B
Vest4		0.14
MVP		0.10
MPC		0.080
ClinPred		0.028	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.43
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs375422080; hg19: chr14-24909432;