dbSNP rs1129093: ZNF75D:p.Thr478Thr (chrX-135287236-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007131.5(ZNF75D):c.1434G>A(p.Thr478Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,209,169 control chromosomes in the GnomAD database, including 59,305 homozygotes. There are 140,186 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 4158 hom., 9121 hem., cov: 23)

Exomes 𝑓: 0.37 ( 55147 hom. 131065 hem. )

Consequence

ZNF75D
NM_007131.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.63

Publications

9 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=-5.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

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.1434G>A	p.Thr478Thr	synonymous	Exon 7 of 7	NP_009062.2
ZNF75D	NM_001185063.2		c.1149G>A	p.Thr383Thr	synonymous	Exon 4 of 4	NP_001171992.1	P51815-2
ZNF75D	NR_110381.2		n.850-31459G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF75D	ENST00000370766.8	TSL:1 MANE Select	c.1434G>A	p.Thr478Thr	synonymous	Exon 7 of 7	ENSP00000359802.3	P51815-1
ZNF75D	ENST00000469456.1	TSL:1	n.1206G>A		non_coding_transcript_exon	Exon 2 of 2
ZNF75D	ENST00000865785.1		c.1434G>A	p.Thr478Thr	synonymous	Exon 7 of 7	ENSP00000535844.1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

31181

AN:

111592

Hom.:

4160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0613

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0444

Gnomad SAS

AF:

0.0993

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.330

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.276

GnomAD2 exomes

AF:

0.299

AC:

54554

AN:

182279

AF XY:

0.297

show subpopulations

Gnomad AFR exome

AF:

0.0551

Gnomad AMR exome

AF:

0.284

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.0420

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.323

GnomAD4 exome

AF:

0.369

AC:

405254

AN:

1097520

Hom.:

55147

Cov.:

AF XY:

0.361

AC XY:

131065

AN XY:

363042

show subpopulations

African (AFR)

AF:

0.0483

AC:

1273

AN:

26370

American (AMR)

AF:

0.279

AC:

9795

AN:

35093

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

6652

AN:

19359

East Asian (EAS)

AF:

0.0414

AC:

1250

AN:

30198

South Asian (SAS)

AF:

0.113

AC:

6093

AN:

54004

European-Finnish (FIN)

AF:

0.376

AC:

15226

AN:

40521

Middle Eastern (MID)

AF:

0.280

AC:

1157

AN:

4134

European-Non Finnish (NFE)

AF:

0.414

AC:

348591

AN:

841766

Other (OTH)

AF:

0.330

AC:

15217

AN:

46075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

9713

19426

29138

38851

48564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11218

22436

33654

44872

56090

<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:

0.279

AC:

31173

AN:

111649

Hom.:

4158

Cov.:

AF XY:

0.269

AC XY:

9121

AN XY:

33871

show subpopulations

African (AFR)

AF:

0.0611

AC:

1888

AN:

30893

American (AMR)

AF:

0.281

AC:

2964

AN:

10561

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

918

AN:

2645

East Asian (EAS)

AF:

0.0445

AC:

159

AN:

3573

South Asian (SAS)

AF:

0.0999

AC:

270

AN:

2702

European-Finnish (FIN)

AF:

0.363

AC:

2155

AN:

5931

Middle Eastern (MID)

AF:

0.333

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.417

AC:

22053

AN:

52931

Other (OTH)

AF:

0.275

AC:

421

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

733

1467

2200

2934

3667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.366

Hom.:

11843

Bravo

AF:

0.265

EpiCase

AF:

0.416

EpiControl

AF:

0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

(source)

DANN

Benign

0.37

PhyloP100

-5.6

Mutation Taster

=100/0

polymorphism (auto)

(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

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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