Variant chrX-135287201-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007131.5(ZNF75D):c.1469C>T(p.Ser490Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,209,495 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 88 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00027 ( 0 hom. 82 hem. )

Consequence

ZNF75D
NM_007131.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08959988).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF75D	NM_007131.5 linkuse as main transcript	c.1469C>T	p.Ser490Leu	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.1469C>T	p.Ser490Leu	missense_variant	7/7	1	NM_007131.5	ENSP00000359802	P2	P51815-1
ZNF75D	ENST00000469456.1 linkuse as main transcript	n.1241C>T		non_coding_transcript_exon_variant	2/2	1
ZNF75D	ENST00000370764.1 linkuse as main transcript	c.1184C>T	p.Ser395Leu	missense_variant	4/4	2		ENSP00000359800	A2	P51815-2
ZNF75D	ENST00000494295.1 linkuse as main transcript	n.828-31424C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

112213

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34381

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000978

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000210

AC:

AN:

181272

Hom.:

AF XY:

0.000167

AC XY:

AN XY:

65896

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:

0.000752

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000266

AC:

292

AN:

1097282

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

AN XY:

362730

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.000617

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000326

GnomAD4 genome

AF:

0.000151

AC:

AN:

112213

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34381

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000978

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000157

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Apr 26, 2023

The c.1469C>T (p.S490L) alteration is located in exon 6 (coding exon 5) of the ZNF75D gene. This alteration results from a C to T substitution at nucleotide position 1469, causing the serine (S) at amino acid position 490 to be replaced by a leucine (L). 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

Pathogenic

0.91

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;.

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.12

Sift

Benign

0.047

D;T

Sift4G

Benign

0.071

T;T

Polyphen

1.0

D;.

Vest4

0.37

MVP

0.68

MPC

0.11

ClinPred

0.17

GERP RS

3.1

Varity_R

0.30

gMVP

0.063

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