Variant chr14-24431904-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015299.3(KHNYN):c.643G>A(p.Ala215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

KHNYN
NM_015299.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

Variant links:

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]

KHNYN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049452573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHNYN	NM_015299.3 linkuse as main transcript	c.643G>A	p.Ala215Thr	missense_variant	3/8	ENST00000553935.6	NP_056114.1	O15037

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KHNYN	ENST00000553935.6 linkuse as main transcript	c.643G>A	p.Ala215Thr	missense_variant	3/8	1	NM_015299.3	ENSP00000450799.1	O15037
KHNYN	ENST00000251343.9 linkuse as main transcript	c.643G>A	p.Ala215Thr	missense_variant	3/8	1		ENSP00000251343.5	O15037
KHNYN	ENST00000556842.5 linkuse as main transcript	c.643G>A	p.Ala215Thr	missense_variant	3/8	2		ENSP00000451106.1	O15037

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250864

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.643G>A (p.A215T) alteration is located in exon 3 (coding exon 2) of the KHNYN gene. This alteration results from a G to A substitution at nucleotide position 643, causing the alanine (A) at amino acid position 215 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

0.075

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.011

T;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.40

.;.;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.96

N;N;N

REVEL

Benign

0.038

Sift

Benign

0.082

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.010

B;B;B

Vest4

0.049

MutPred

0.14

Loss of stability (P = 0.0389);Loss of stability (P = 0.0389);Loss of stability (P = 0.0389);

MVP

0.28

MPC

0.25

ClinPred

0.045

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over