dbSNP rs1261329316: ZNF75D:p.Asn284His (chrX-135287820-T-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.850A>C(p.Asn284His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,205,340 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 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 0.000036 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000031 ( 0 hom. 18 hem. )

Consequence

ZNF75D
NM_007131.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0440

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=0.1317718).

BS2

High Hemizygotes in GnomAdExome4 at 18 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.850A>C	p.Asn284His	missense	Exon 7 of 7	NP_009062.2
ZNF75D	NM_001185063.2		c.565A>C	p.Asn189His	missense	Exon 4 of 4	NP_001171992.1	P51815-2
ZNF75D	NR_110381.2		n.850-32043A>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF75D	ENST00000370766.8	TSL:1 MANE Select	c.850A>C	p.Asn284His	missense	Exon 7 of 7	ENSP00000359802.3	P51815-1
ZNF75D	ENST00000469456.1	TSL:1	n.622A>C		non_coding_transcript_exon	Exon 2 of 2
ZNF75D	ENST00000865785.1		c.850A>C	p.Asn284His	missense	Exon 7 of 7	ENSP00000535844.1

Frequencies

GnomAD3 genomes

AF:

0.0000355

AC:

AN:

112593

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:

0.0000750

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000226

AC:

AN:

177328

AF XY:

0.0000479

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:

0.0000250

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.0000311

AC:

AN:

1092747

Hom.:

Cov.:

AF XY:

0.0000502

AC XY:

AN XY:

358591

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26146

American (AMR)

AF:

0.0000291

AC:

AN:

34343

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19259

East Asian (EAS)

AF:

0.00

AC:

AN:

30179

South Asian (SAS)

AF:

0.0000188

AC:

AN:

53257

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40398

Middle Eastern (MID)

AF:

0.000729

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.0000262

AC:

AN:

839128

Other (OTH)

AF:

0.000152

AC:

AN:

45921

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.0000355

AC:

AN:

112593

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34739

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30973

American (AMR)

AF:

0.00

AC:

AN:

10618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3610

South Asian (SAS)

AF:

0.00

AC:

AN:

2757

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6181

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000750

AC:

AN:

53351

Other (OTH)

AF:

0.00

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.0000453

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

0.12

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.97

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.65

M_CAP

Benign

0.00093

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

0.044

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.019

Sift

Uncertain

0.017

Sift4G

Uncertain

0.029

Polyphen

0.22

Vest4

0.070

MutPred

0.38

Loss of loop (P = 0.0112)

MVP

0.74

MPC

0.34

ClinPred

0.096

GERP RS

1.7

Varity_R

0.16

gMVP

0.084

Mutation Taster

=98/2

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