chr14-24440174-C-T

Variant names:

• chr14-24440174-C-T
• rs750740557
• NM_020195.3:c.791G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_020195.3(SDR39U1):​c.791G>A​(p.Gly264Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000226 in 1,461,486 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: 0.000023 (0 hom.)
• Consequence: SDR39U1 NM_020195.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

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.791G>A	p.Gly264Asp	missense	Exon 6 of 6	NP_064580.2	Q9NRG7-2
	KHNYN	NM_015299.3	MANE Select	c.*2889C>T		3_prime_UTR	Exon 8 of 8	NP_056114.1	O15037
	SDR39U1	NM_001387322.1		c.860G>A	p.Gly287Asp	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.791G>A	p.Gly264Asp	missense	Exon 6 of 6	ENSP00000382327.3	Q9NRG7-2
	SDR39U1	ENST00000554698.5	TSL:1	c.467G>A	p.Gly156Asp	missense	Exon 4 of 4	ENSP00000452438.1	Q86TZ5
	KHNYN	ENST00000553935.6	TSL:1 MANE Select	c.*2889C>T		3_prime_UTR	Exon 8 of 8	ENSP00000450799.1	O15037

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000366 AC: 9 AN: 246210 AF XY: 0.0000224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000390

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461486 Hom.: 0 Cov.: 68 AF XY: 0.0000206 AC XY: 15 AN XY: 727004

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111760

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

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	Pathogenic	0.79
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.059	D
PhyloP100		7.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.027	D
Polyphen		0.95	P
Vest4		0.91
MVP		0.61
MPC		0.50
ClinPred		0.85	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.84
Mutation Taster		=35/65	disease causing

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

Other links and lift over

dbSNP: rs750740557; hg19: chr14-24909380;