Variant chr14-23522057-A-T 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_033400.3(ZFHX2):c.7624T>A(p.Ser2542Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 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)

Consequence

ZFHX2
NM_033400.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

Variant links:

Genes affected

ZFHX2 (HGNC:20152): (zinc finger homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of sensory perception of pain. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFHX2 links:

ZFHX2-AS1 (HGNC:52658): (ZFHX2 antisense RNA 1)

ZFHX2-AS1 links:

THTPA (HGNC:):

THTPA links:

Genome browser will be placed here

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=0.025573403).

BP6

Variant 14-23522057-A-T is Benign according to our data. Variant chr14-23522057-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2534766.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX2	NM_033400.3 linkuse as main transcript	c.7624T>A	p.Ser2542Thr	missense_variant	10/10	ENST00000419474.5	NP_207646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX2	ENST00000419474.5 linkuse as main transcript	c.7624T>A	p.Ser2542Thr	missense_variant	10/10	5	NM_033400.3	ENSP00000413418	P1	Q9C0A1-1
ZFHX2-AS1	ENST00000553985.1 linkuse as main transcript	n.238+7641A>T		intron_variant, non_coding_transcript_variant		2
ZFHX2-AS1	ENST00000554403.1 linkuse as main transcript	n.1068+7641A>T		intron_variant, non_coding_transcript_variant		2
ZFHX2-AS1	ENST00000556354.5 linkuse as main transcript	n.465+7641A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Apr 07, 2023

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

0.058

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.31

DANN

Benign

0.83

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.48

M_CAP

Benign

0.014

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.49

REVEL

Benign

0.25

Sift

Benign

1.0

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.067

MutPred

0.36

Gain of catalytic residue at T2539 (P = 0.0055);

MVP

0.11

ClinPred

0.030

GERP RS

-0.80

Varity_R

0.051

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over