Genetic Variant ZNF75D:p.Ser431Thr (chrX-135287378-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007131.5(ZNF75D):c.1292G>C(p.Ser431Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,210,127 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 48 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00015 ( 0 hom. 46 hem. )

Consequence

ZNF75D
NM_007131.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.321

Publications

0 publications found

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:

ETDC (HGNC:53450): (embryonic testis differentiation homolog C)

ETDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14841303).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007131.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF75D	NM_007131.5	MANE Select	c.1292G>C	p.Ser431Thr	missense	Exon 7 of 7	NP_009062.2
ZNF75D	NM_001185063.2		c.1007G>C	p.Ser336Thr	missense	Exon 4 of 4	NP_001171992.1	P51815-2
ZNF75D	NR_110381.2		n.850-31601G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF75D	ENST00000370766.8	TSL:1 MANE Select	c.1292G>C	p.Ser431Thr	missense	Exon 7 of 7	ENSP00000359802.3	P51815-1
ZNF75D	ENST00000469456.1	TSL:1	n.1064G>C		non_coding_transcript_exon	Exon 2 of 2
ZNF75D	ENST00000865785.1		c.1292G>C	p.Ser431Thr	missense	Exon 7 of 7	ENSP00000535844.1

Frequencies

GnomAD3 genomes

AF:

0.0000623

AC:

AN:

112378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000647

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000939

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000546

AC:

AN:

183152

AF XY:

0.0000148

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 FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.0000856

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000151

AC:

166

AN:

1097749

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

363129

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26391

American (AMR)

AF:

0.00

AC:

AN:

35184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.00

AC:

AN:

54106

European-Finnish (FIN)

AF:

0.0000493

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4087

European-Non Finnish (NFE)

AF:

0.000190

AC:

160

AN:

841801

Other (OTH)

AF:

0.0000868

AC:

AN:

46065

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000623

AC:

AN:

112378

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

34542

show subpopulations

African (AFR)

AF:

0.0000647

AC:

AN:

30896

American (AMR)

AF:

0.00

AC:

AN:

10634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3614

South Asian (SAS)

AF:

0.00

AC:

AN:

2720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000939

AC:

AN:

53247

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-1.0

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

FATHMM_MKL

Benign

0.00039

LIST_S2

Benign

0.61

M_CAP

Benign

0.0012

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.18

PhyloP100

-0.32

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.039

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

0.28

Vest4

0.073

MVP

0.76

MPC

0.35

ClinPred

0.23

GERP RS

1.9

Varity_R

0.61

gMVP

0.040

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over