Variant 7-64348224-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_001170905.3(ZNF736):c.361G>A(p.Gly121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,551,818 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZNF736
NM_001170905.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.450

Variant links:

Genes affected

ZNF736 (HGNC:32467): (zinc finger protein 736) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF736 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=0.030897677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF736	NM_001170905.3 linkuse as main transcript	c.361G>A	p.Gly121Ser	missense_variant	4/4	ENST00000423484.3	NP_001164376.1	B4DX44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF736	ENST00000423484.3 linkuse as main transcript	c.361G>A	p.Gly121Ser	missense_variant	4/4	2	NM_001170905.3	ENSP00000400852.1		B4DX44
ZNF736	ENST00000355095.8 linkuse as main transcript	c.361G>A	p.Gly121Ser	missense_variant	5/5	5		ENSP00000347210.4		B4DX44

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000506

AC:

AN:

158176

Hom.:

AF XY:

0.0000360

AC XY:

AN XY:

83306

show subpopulations

Gnomad AFR exome

AF:

0.000120

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000588

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000446

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1399580

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690284

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000688

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ExAC

AF:

0.0000377

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

Jul 14, 2024

The c.361G>A (p.G121S) alteration is located in exon 5 (coding exon 4) of the ZNF736 gene. This alteration results from a G to A substitution at nucleotide position 361, causing the glycine (G) at amino acid position 121 to be replaced by a serine (S). 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

-0.54

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.14

T;.

M_CAP

Benign

0.00092

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.84

L;L

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.020

Sift

Benign

0.092

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0030

B;B

Vest4

0.097

MutPred

0.20

Gain of disorder (P = 0.1071);Gain of disorder (P = 0.1071);

MVP

0.061

MPC

0.050

ClinPred

0.0082

GERP RS

-0.13

Varity_R

0.048

gMVP

0.045

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