rs1129093

Variant names:

• chrX-135287236-C-T
• rs1129093
• NM_007131.5:c.1434G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.63

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF75D	NM_007131.5	c.1434G>A	p.Thr478Thr	synonymous_variant	Exon 7 of 7	ENST00000370766.8	NP_009062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF75D	ENST00000370766.8	c.1434G>A	p.Thr478Thr	synonymous_variant	Exon 7 of 7	1	NM_007131.5	ENSP00000359802.3
ZNF75D	ENST00000469456.1	n.1206G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
ZNF75D	ENST00000370764.1	c.1149G>A	p.Thr383Thr	synonymous_variant	Exon 4 of 4	2		ENSP00000359800.1
ZNF75D	ENST00000494295.1	n.828-31459G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 31181 AN: 111592 Hom.: 4160 Cov.: 23

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

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.: 33 AF XY: 0.361 AC XY: 131065 AN XY: 363042

Gnomad4 AFR exome AF: 0.0483 AC: 1273 AN: 26370

Gnomad4 AMR exome AF: 0.279 AC: 9795 AN: 35093

Gnomad4 ASJ exome AF: 0.344 AC: 6652 AN: 19359

Gnomad4 EAS exome AF: 0.0414 AC: 1250 AN: 30198

Gnomad4 SAS exome AF: 0.113 AC: 6093 AN: 54004

Gnomad4 FIN exome AF: 0.376 AC: 15226 AN: 40521

Gnomad4 NFE exome AF: 0.414 AC: 348591 AN: 841766

Gnomad4 Remaining exome AF: 0.330 AC: 15217 AN: 46075

GnomAD4 genome AF: 0.279 AC: 31173 AN: 111649 Hom.: 4158 Cov.: 23 AF XY: 0.269 AC XY: 9121 AN XY: 33871

Gnomad4 AFR AF: 0.0611 AC: 0.0611142 AN: 0.0611142

Gnomad4 AMR AF: 0.281 AC: 0.280655 AN: 0.280655

Gnomad4 ASJ AF: 0.347 AC: 0.34707 AN: 0.34707

Gnomad4 EAS AF: 0.0445 AC: 0.0445004 AN: 0.0445004

Gnomad4 SAS AF: 0.0999 AC: 0.099926 AN: 0.099926

Gnomad4 FIN AF: 0.363 AC: 0.363345 AN: 0.363345

Gnomad4 NFE AF: 0.417 AC: 0.416637 AN: 0.416637

Gnomad4 OTH AF: 0.275 AC: 0.275343 AN: 0.275343

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1129093; hg19: chrX-134421168; COSMIC: COSV66132332;