14-24441679-C-G

Variant names:

• chr14-24441679-C-G
• rs1372450040
• NM_020195.3:c.323G>C

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>C variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000279 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: 0.0000028 (0 hom.)
• Consequence: SDR39U1 NM_001387324.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• 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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR39U1	NM_020195.3	MANE Select	c.323G>C	p.Gly108Ala	missense	Exon 4 of 6	NP_064580.2	Q9NRG7-2
	KHNYN	NM_015299.3	MANE Select	c.*4394C>G		3_prime_UTR	Exon 8 of 8	NP_056114.1	O15037
	SDR39U1	NM_001387322.1		c.392G>C	p.Gly131Ala	missense	Exon 4 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.323G>C	p.Gly108Ala	missense	Exon 4 of 6	ENSP00000382327.3	Q9NRG7-2
	KHNYN	ENST00000553935.6	TSL:1 MANE Select	c.*4394C>G		3_prime_UTR	Exon 8 of 8	ENSP00000450799.1	O15037
	KHNYN	ENST00000251343.9	TSL:1	c.*4394C>G		3_prime_UTR	Exon 8 of 8	ENSP00000251343.5	O15037

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000905 AC: 2 AN: 221022 AF XY: 0.0000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1431410 Hom.: 0 Cov.: 40 AF XY: 0.00000281 AC XY: 2 AN XY: 712244

African (AFR) AF: 0.00 AC: 0 AN: 31330

American (AMR) AF: 0.00 AC: 0 AN: 33528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24642

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 81286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5304

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1103408

Other (OTH) AF: 0.00 AC: 0 AN: 59066

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.069	T
PhyloP100		7.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Pathogenic	0.71
Sift	Benign	0.079	T
Sift4G	Benign	0.50	T
Polyphen		0.97	D
Vest4		0.74
MVP		0.69
MPC		0.18
ClinPred		0.93	D
GERP RS		5.5
gMVP		0.86
Mutation Taster		=173/127	polymorphism

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: rs1372450040; hg19: chr14-24910885;