X-135287570-C-G

Variant names:

• chrX-135287570-C-G
• rs782539023
• NM_007131.5:c.1100G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007131.5(ZNF75D):​c.1100G>C​(p.Cys367Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,773 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: ZNF75D NM_007131.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.05

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF75D	NM_007131.5	c.1100G>C	p.Cys367Ser	missense_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.1100G>C	p.Cys367Ser	missense_variant	Exon 7 of 7	1	NM_007131.5	ENSP00000359802.3
ZNF75D	ENST00000469456.1	n.872G>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
ZNF75D	ENST00000370764.1	c.815G>C	p.Cys272Ser	missense_variant	Exon 4 of 4	2		ENSP00000359800.1
ZNF75D	ENST00000494295.1	n.828-31793G>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000548 AC: 1 AN: 182415 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67061

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000726

Gnomad SAS 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: 0.00000182 AC: 2 AN: 1097773 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363161

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000662

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.59
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.
FATHMM_MKL	Benign	0.064	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Pathogenic	4.3	H;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-9.5	D;D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.97	D;.
Vest4		0.58
MutPred		0.84		Gain of phosphorylation at C367 (P = 0.0313);.;
MVP		0.69
MPC		0.65
ClinPred		1.0	D
GERP RS		2.2
Varity_R		0.91
gMVP		0.53

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: rs782539023; hg19: chrX-134421502;