14-24431899-G-C

Position:

• chr14-24431899-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015299.3(KHNYN):​c.638G>C​(p.Ser213Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: 0.312

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07620096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHNYN	NM_015299.3	c.638G>C	p.Ser213Thr	missense_variant	3/8	ENST00000553935.6	NP_056114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHNYN	ENST00000553935.6	c.638G>C	p.Ser213Thr	missense_variant	3/8	1	NM_015299.3	ENSP00000450799.1
KHNYN	ENST00000251343.9	c.638G>C	p.Ser213Thr	missense_variant	3/8	1		ENSP00000251343.5
KHNYN	ENST00000556842.5	c.638G>C	p.Ser213Thr	missense_variant	3/8	2		ENSP00000451106.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.638G>C (p.S213T) alteration is located in exon 3 (coding exon 2) of the KHNYN gene. This alteration results from a G to C substitution at nucleotide position 638, causing the serine (S) at amino acid position 213 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.1
DANN	Benign	0.89
DEOGEN2	Benign	0.016	T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.29	.;.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.13	N;N;N
REVEL	Benign	0.036
Sift	Uncertain	0.024	D;D;D
Sift4G	Benign	0.61	T;T;T
Polyphen		0.015	B;B;B
Vest4		0.23
MutPred		0.14		Loss of phosphorylation at S213 (P = 0.0695);Loss of phosphorylation at S213 (P = 0.0695);Loss of phosphorylation at S213 (P = 0.0695);
MVP		0.39
MPC		0.29
ClinPred		0.057	T
GERP RS		1.1
Varity_R		0.068
gMVP		0.36

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24901105;