X-135292341-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007131.5(ZNF75D):​c.544G>A​(p.Val182Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,101 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V182L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: ZNF75D NM_007131.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28685832).

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>A	p.Val182Ile	missense	Exon 4 of 7	NP_009062.2
	ZNF75D	NM_001185063.2		c.412-1206G>A		intron	N/A	NP_001171992.1	P51815-2
	ZNF75D	NR_110381.2		n.850-36564G>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.544G>A	p.Val182Ile	missense	Exon 4 of 7	ENSP00000359802.3	P51815-1
	ZNF75D	ENST00000865785.1		c.544G>A	p.Val182Ile	missense	Exon 4 of 7	ENSP00000535844.1
	ZNF75D	ENST00000865786.1		c.544G>A	p.Val182Ile	missense	Exon 3 of 6	ENSP00000535845.1

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112101 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112101 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34283

African (AFR) AF: 0.0000325 AC: 1 AN: 30808

American (AMR) AF: 0.00 AC: 0 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.9
DANN	Benign	0.87
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.00082	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.10
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.048
Sift	Benign	0.30	T
Sift4G	Benign	0.98	T
Polyphen		1.0	D
Vest4		0.12
MutPred		0.40		Loss of MoRF binding (P = 0.1091)
MVP		0.64
MPC		0.11
ClinPred		0.21	T
GERP RS		2.3
Varity_R		0.059
gMVP		0.23
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;