14-24431641-C-A

Variant names:

• chr14-24431641-C-A
• rs1190723807
• NM_015299.3:c.380C>A

Variant summary

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

The NM_015299.3(KHNYN):​c.380C>A​(p.Ala127Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KHNYN NM_015299.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.55
• Publications: 0 publications found

Genes affected

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_015299.3. 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
	KHNYN	NM_015299.3	MANE Select	c.380C>A	p.Ala127Asp	missense	Exon 3 of 8	NP_056114.1	O15037
	KHNYN	NM_001290256.2		c.503C>A	p.Ala168Asp	missense	Exon 3 of 8	NP_001277185.1
	KHNYN	NM_001290257.2		c.380C>A	p.Ala127Asp	missense	Exon 3 of 8	NP_001277186.1	O15037

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHNYN	ENST00000553935.6	TSL:1 MANE Select	c.380C>A	p.Ala127Asp	missense	Exon 3 of 8	ENSP00000450799.1	O15037
	KHNYN	ENST00000251343.9	TSL:1	c.380C>A	p.Ala127Asp	missense	Exon 3 of 8	ENSP00000251343.5	O15037
	KHNYN	ENST00000556842.5	TSL:2	c.380C>A	p.Ala127Asp	missense	Exon 3 of 8	ENSP00000451106.1	O15037

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.047	D
Polyphen		0.96	D
Vest4		0.90
MutPred		0.50		Gain of catalytic residue at L124 (P = 6e-04)
MVP		0.75
MPC		1.1
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.71
gMVP		0.63
Mutation Taster		=90/10	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: rs1190723807; hg19: chr14-24900847;