chr14-24440205-C-T

Variant names:

• chr14-24440205-C-T
• rs372475511
• NM_020195.3:c.760G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20
• 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: Uncertain_significance. The variant received 4 ACMG points.

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

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.760G>A	p.Gly254Arg	missense	Exon 6 of 6	NP_064580.2	Q9NRG7-2
	KHNYN	NM_015299.3	MANE Select	c.*2920C>T		3_prime_UTR	Exon 8 of 8	NP_056114.1	O15037
	SDR39U1	NM_001387322.1		c.829G>A	p.Gly277Arg	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.760G>A	p.Gly254Arg	missense	Exon 6 of 6	ENSP00000382327.3	Q9NRG7-2
	SDR39U1	ENST00000554698.5	TSL:1	c.436G>A	p.Gly146Arg	missense	Exon 4 of 4	ENSP00000452438.1	Q86TZ5
	KHNYN	ENST00000553935.6	TSL:1 MANE Select	c.*2920C>T		3_prime_UTR	Exon 8 of 8	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

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

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111820

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 34

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	0.70
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.27	D
PhyloP100		7.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	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
Mutation Taster		=41/59	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: rs372475511; hg19: chr14-24909411;