X-135292341-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF75D	NM_007131.5	c.544G>A	p.Val182Ile	missense_variant	Exon 4 of 7	ENST00000370766.8	NP_009062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF75D	ENST00000370766.8	c.544G>A	p.Val182Ile	missense_variant	Exon 4 of 7	1	NM_007131.5	ENSP00000359802.3
ZNF75D	ENST00000370764.1	c.412-1206G>A		intron_variant	Intron 2 of 3	2		ENSP00000359800.1
ZNF75D	ENST00000494295.1	n.828-36564G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112101 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34283

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

Gnomad4 AFR AF: 0.0000325

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs782234936; hg19: chrX-134426267;