chrX-135292341-C-G

Variant names:

• chrX-135292341-C-G
• rs782234936
• NM_007131.5:c.544G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_007131.5(ZNF75D):​c.544G>C​(p.Val182Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,209,999 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 4 hem.)
• Consequence: ZNF75D NM_007131.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.103
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17835018).
• BS2: High Hemizygotes in GnomAdExome4 at 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF75D	NM_007131.5	MANE Select	c.544G>C	p.Val182Leu	missense	Exon 4 of 7	NP_009062.2
	ZNF75D	NM_001185063.2		c.412-1206G>C		intron	N/A	NP_001171992.1	P51815-2
	ZNF75D	NR_110381.2		n.850-36564G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF75D	ENST00000370766.8	TSL:1 MANE Select	c.544G>C	p.Val182Leu	missense	Exon 4 of 7	ENSP00000359802.3	P51815-1
	ZNF75D	ENST00000865785.1		c.544G>C	p.Val182Leu	missense	Exon 4 of 7	ENSP00000535844.1
	ZNF75D	ENST00000865786.1		c.544G>C	p.Val182Leu	missense	Exon 3 of 6	ENSP00000535845.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112101 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000188

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000654 AC: 12 AN: 183408 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000438

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1097898 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 4 AN XY: 363286

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.000341 AC: 12 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54125

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4035

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841940

Other (OTH) AF: 0.00 AC: 0 AN: 46076

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112101 Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1 AN XY: 34283

African (AFR) AF: 0.00 AC: 0 AN: 30808

American (AMR) AF: 0.000188 AC: 2 AN: 10614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3599

South Asian (SAS) AF: 0.00 AC: 0 AN: 2693

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6117

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53204

Other (OTH) AF: 0.00 AC: 0 AN: 1498

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.54
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.10
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.047
Sift	Benign	0.31	T
Sift4G	Benign	0.84	T
Polyphen		1.0	D
Vest4		0.10
MutPred		0.40		Loss of MoRF binding (P = 0.085)
MVP		0.79
MPC		0.13
ClinPred		0.056	T
GERP RS		2.3
Varity_R		0.092
gMVP		0.42
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782234936; hg19: chrX-134426267;