Variant 14-24431958-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.697G>A(p.Glu233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,312 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000090 ( 1 hom. )

Consequence

KHNYN
NM_015299.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.389

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=0.030731022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHNYN	NM_015299.3 linkuse as main transcript	c.697G>A	p.Glu233Lys	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.697G>A	p.Glu233Lys	missense_variant	3/8	1	NM_015299.3	ENSP00000450799.1	O15037
KHNYN	ENST00000251343.9 linkuse as main transcript	c.697G>A	p.Glu233Lys	missense_variant	3/8	1		ENSP00000251343.5	O15037
KHNYN	ENST00000556842.5 linkuse as main transcript	c.697G>A	p.Glu233Lys	missense_variant	3/8	2		ENSP00000451106.1	O15037

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

250554

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000897

AC:

131

AN:

1461002

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000538

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000918

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000593

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

May 31, 2023

The c.697G>A (p.E233K) 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 697, causing the glutamic acid (E) at amino acid position 233 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.70

.;.;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.083

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.71

T;T;T

Polyphen

0.28

B;B;B

Vest4

0.14

MVP

0.39

MPC

0.29

ClinPred

0.061

GERP RS

5.0

Varity_R

0.23

gMVP

0.56

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

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