Variant 12-48343597-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001172681.2(ZNF641):c.651C>G(p.Ser217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,786 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF641
NM_001172681.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.38

Variant links:

Genes affected

ZNF641 (HGNC:31834): (zinc finger protein 641) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF641 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=0.033498615).

BP6

Variant 12-48343597-G-C is Benign according to our data. Variant chr12-48343597-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3197398.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF641	NM_001172681.2 linkuse as main transcript	c.651C>G	p.Ser217Arg	missense_variant	6/6	ENST00000547026.6	NP_001166152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF641	ENST00000547026.6 linkuse as main transcript	c.651C>G	p.Ser217Arg	missense_variant	6/6	1	NM_001172681.2	ENSP00000449974	P1	Q96N77-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245100

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000138

AC:

AN:

1452786

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000457

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.57

DANN

Benign

0.30

DEOGEN2

Benign

0.00036

T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.34

.;T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.14

N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.24

N;N;N;N

REVEL

Benign

0.010

Sift

Benign

0.71

T;T;T;T

Sift4G

Benign

0.61

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.17

MutPred

0.18

Loss of phosphorylation at S231 (P = 0.0188);Loss of phosphorylation at S231 (P = 0.0188);.;.;

MVP

0.14

MPC

0.26

ClinPred

0.018

GERP RS

-3.1

Varity_R

0.045

gMVP

0.16

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