Variant X-135287769-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007131.5(ZNF75D):c.901G>A(p.Glu301Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,208,466 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.00010 ( 0 hom. 38 hem. )

Consequence

ZNF75D
NM_007131.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.607

Variant links:

Genes affected

ZNF75D (HGNC:13145): (zinc finger protein 75D) This gene encodes a protein that likely functions as a transcription factor. The protein, which belongs to the ZNF75 family, includes an N-terminal SCAN domain, a KRAB box, and five C2H2-type zinc finger motifs. Another functional gene belonging to this family is located on chromosome 16, while pseudogenes have been identified on chromosomes 11 and 12. Alternative splicing results in multiple transcripts variants. [provided by RefSeq, Jun 2010]

ZNF75D links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031093001).

BP6

Variant X-135287769-C-T is Benign according to our data. Variant chrX-135287769-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2380037.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-135287769-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF75D	NM_007131.5 linkuse as main transcript	c.901G>A	p.Glu301Lys	missense_variant	7/7	ENST00000370766.8	NP_009062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF75D	ENST00000370766.8 linkuse as main transcript	c.901G>A	p.Glu301Lys	missense_variant	7/7	1	NM_007131.5	ENSP00000359802	P2	P51815-1
ZNF75D	ENST00000469456.1 linkuse as main transcript	n.673G>A		non_coding_transcript_exon_variant	2/2	1
ZNF75D	ENST00000370764.1 linkuse as main transcript	c.616G>A	p.Glu206Lys	missense_variant	4/4	2		ENSP00000359800	A2	P51815-2
ZNF75D	ENST00000494295.1 linkuse as main transcript	n.828-31992G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000205

AC:

AN:

112458

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

34640

show subpopulations

Gnomad AFR

AF:

0.000452

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

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:

0.0000938

Gnomad OTH

AF:

0.000658

GnomAD3 exomes

AF:

0.000111

AC:

AN:

180924

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

65680

show subpopulations

Gnomad AFR exome

AF:

0.000229

Gnomad AMR exome

AF:

0.000149

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:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

113

AN:

1095952

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

361504

show subpopulations

Gnomad4 AFR exome

AF:

0.0000761

Gnomad4 AMR exome

AF:

0.000288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000374

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.000204

AC:

AN:

112514

Hom.:

Cov.:

AF XY:

0.0000864

AC XY:

AN XY:

34706

show subpopulations

Gnomad4 AFR

AF:

0.000451

Gnomad4 AMR

AF:

0.000282

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000938

Gnomad4 OTH

AF:

0.000650

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000234

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

May 27, 2022

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

0.076

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.22

DANN

Benign

0.30

DEOGEN2

Benign

0.023

T;.

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.10

T;T

M_CAP

Benign

0.00053

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.49

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.0090

Sift

Benign

0.96

T;T

Sift4G

Benign

0.84

T;T

Polyphen

0.0

B;.

Vest4

0.038

MVP

0.58

MPC

0.14

ClinPred

0.017

GERP RS

-1.7

Varity_R

0.051

gMVP

0.17

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