Genetic Variant ZNF75D:p.Cys505Arg (chrX-135287157-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_007131.5(ZNF75D):c.1513T>C(p.Cys505Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,205,753 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Consequence

ZNF75D
NM_007131.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34846735).

BS2

High Hemizygotes in GnomAdExome4 at 7 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.1513T>C	p.Cys505Arg	missense	Exon 7 of 7	NP_009062.2
ZNF75D	NM_001185063.2		c.1228T>C	p.Cys410Arg	missense	Exon 4 of 4	NP_001171992.1	P51815-2
ZNF75D	NR_110381.2		n.850-31380T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF75D	ENST00000370766.8	TSL:1 MANE Select	c.1513T>C	p.Cys505Arg	missense	Exon 7 of 7	ENSP00000359802.3	P51815-1
ZNF75D	ENST00000469456.1	TSL:1	n.1285T>C		non_coding_transcript_exon	Exon 2 of 2
ZNF75D	ENST00000865785.1		c.1513T>C	p.Cys505Arg	missense	Exon 7 of 7	ENSP00000535844.1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112379

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000567

AC:

AN:

176270

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1093374

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

360172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26028

American (AMR)

AF:

0.00

AC:

AN:

33880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19214

East Asian (EAS)

AF:

0.00

AC:

AN:

30177

South Asian (SAS)

AF:

0.00

AC:

AN:

52911

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.0000262

AC:

AN:

840632

Other (OTH)

AF:

0.00

AC:

AN:

45915

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

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:

0.0000178

AC:

AN:

112379

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34525

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30877

American (AMR)

AF:

0.00

AC:

AN:

10601

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3598

South Asian (SAS)

AF:

0.00

AC:

AN:

2737

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6193

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

53278

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000151

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

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.088

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.59

M_CAP

Benign

0.0017

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

PhyloP100

2.8

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.2

REVEL

Benign

0.071

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.54

MutPred

0.49

Gain of MoRF binding (P = 2e-04)

MVP

0.45

MPC

0.26

ClinPred

0.93

GERP RS

3.1

Varity_R

0.84

gMVP

0.12

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over