Variant 2-71349343-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_014497.5(ZNF638):c.389A>G(p.Lys130Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF638
NM_014497.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

Variant links:

Genes affected

ZNF638 (HGNC:17894): (zinc finger protein 638) The protein encoded by this gene is a nucleoplasmic protein. It binds cytidine-rich sequences in double-stranded DNA. This protein has three types of domains: MH1, MH2 (repeated three times) and MH3. It is associated with packaging, transferring, or processing transcripts. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

ZNF638 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.074528456).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF638	NM_014497.5 linkuse as main transcript	c.389A>G	p.Lys130Arg	missense_variant	2/28	ENST00000264447.9
ZNF638	NM_001014972.3 linkuse as main transcript	c.389A>G	p.Lys130Arg	missense_variant	2/28
ZNF638	NM_001252612.2 linkuse as main transcript	c.389A>G	p.Lys130Arg	missense_variant	2/28
ZNF638	NM_001252613.2 linkuse as main transcript	c.389A>G	p.Lys130Arg	missense_variant	2/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF638	ENST00000264447.9 linkuse as main transcript	c.389A>G	p.Lys130Arg	missense_variant	2/28	1	NM_014497.5	P1	Q14966-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 19, 2023

The c.389A>G (p.K130R) alteration is located in exon 2 (coding exon 1) of the ZNF638 gene. This alteration results from a A to G substitution at nucleotide position 389, causing the lysine (K) at amino acid position 130 to be replaced by an arginine (R). 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

0.083

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.11

Eigen_PC

Benign

0.056

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.79

T;T;.;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.075

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.31

REVEL

Benign

0.053

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.52

.;.;P;P

Vest4

0.042

MutPred

0.20

Loss of ubiquitination at K130 (P = 9e-04);Loss of ubiquitination at K130 (P = 9e-04);Loss of ubiquitination at K130 (P = 9e-04);Loss of ubiquitination at K130 (P = 9e-04);

MVP

0.15

MPC

0.035

ClinPred

0.23

GERP RS

4.3

Varity_R

0.046

gMVP

0.068

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