X-135291484-C-T

Variant names:

• chrX-135291484-C-T
• rs78544936
• NM_007131.5:c.684G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007131.5(ZNF75D):​c.684G>A​(p.Leu228Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,210,384 control chromosomes in the GnomAD database, including 79 homozygotes. There are 1,037 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (50 hom., 489 hem., cov: 23)
  • Exomes 𝑓: 0.0019 (29 hom. 548 hem.)
• Consequence: ZNF75D NM_007131.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-135291484-C-T is Benign according to our data. Variant chrX-135291484-C-T is described in ClinVar as Benign. ClinVar VariationId is 781644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0552 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF75D	NM_007131.5	MANE Select	c.684G>A	p.Leu228Leu	synonymous	Exon 5 of 7	NP_009062.2
	ZNF75D	NM_001185063.2		c.412-349G>A		intron	N/A	NP_001171992.1	P51815-2
	ZNF75D	NR_110381.2		n.850-35707G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF75D	ENST00000370766.8	TSL:1 MANE Select	c.684G>A	p.Leu228Leu	synonymous	Exon 5 of 7	ENSP00000359802.3	P51815-1
	ZNF75D	ENST00000469456.1	TSL:1	n.120G>A		non_coding_transcript_exon	Exon 1 of 2
	ZNF75D	ENST00000865785.1		c.684G>A	p.Leu228Leu	synonymous	Exon 5 of 7	ENSP00000535844.1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 1901 AN: 112328 Hom.: 49 Cov.: 23

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00889

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: 0.000188

Gnomad OTH AF: 0.0159

GnomAD2 exomes AF: 0.00518 AC: 948 AN: 182933 AF XY: 0.00346

Gnomad AFR exome AF: 0.0623

Gnomad AMR exome AF: 0.00377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000981

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00192 AC: 2104 AN: 1098004 Hom.: 29 Cov.: 30 AF XY: 0.00151 AC XY: 548 AN XY: 363360

African (AFR) AF: 0.0641 AC: 1691 AN: 26391

American (AMR) AF: 0.00421 AC: 148 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.000166 AC: 9 AN: 54111

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.00242 AC: 10 AN: 4137

European-Non Finnish (NFE) AF: 0.0000356 AC: 30 AN: 841985

Other (OTH) AF: 0.00469 AC: 216 AN: 46087

GnomAD4 genome AF: 0.0169 AC: 1903 AN: 112380 Hom.: 50 Cov.: 23 AF XY: 0.0142 AC XY: 489 AN XY: 34538

African (AFR) AF: 0.0574 AC: 1774 AN: 30894

American (AMR) AF: 0.00888 AC: 95 AN: 10700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.00 AC: 0 AN: 2675

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000188 AC: 10 AN: 53259

Other (OTH) AF: 0.0157 AC: 24 AN: 1533

Alfa AF: 0.00938 Hom.: 55

Bravo AF: 0.0208

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78544936; hg19: chrX-134425410;