Variant chr7-64348587-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170905.3(ZNF736):c.724T>A(p.Ser242Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000694 in 1,441,122 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: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ZNF736
NM_001170905.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.197

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15161493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF736	NM_001170905.3 linkuse as main transcript	c.724T>A	p.Ser242Thr	missense_variant	4/4	ENST00000423484.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF736	ENST00000423484.3 linkuse as main transcript	c.724T>A	p.Ser242Thr	missense_variant	4/4	2	NM_001170905.3	P1
ZNF736	ENST00000355095.8 linkuse as main transcript	c.724T>A	p.Ser242Thr	missense_variant	5/5	5		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000462

AC:

AN:

216588

Hom.:

AF XY:

0.00000855

AC XY:

AN XY:

116996

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000694

AC:

AN:

1441122

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

715298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000241

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:

0.00000545

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000828

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

Aug 21, 2023

The c.724T>A (p.S242T) alteration is located in exon 5 (coding exon 4) of the ZNF736 gene. This alteration results from a T to A substitution at nucleotide position 724, causing the serine (S) at amino acid position 242 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

0.28

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.00056

LIST_S2

Uncertain

0.87

D;.

M_CAP

Benign

0.0011

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.068

Sift

Benign

0.072

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.99

D;D

Vest4

0.080

MutPred

0.52

Gain of glycosylation at S242 (P = 0.0532);Gain of glycosylation at S242 (P = 0.0532);

MVP

0.030

MPC

0.047

ClinPred

0.18

GERP RS

1.1

Varity_R

0.085

gMVP

0.010

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