NM_007157.4:c.222G>A

Variant names:

• chrX-57592270-G-A
• rs768201846
• NM_007157.4:c.222G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007157.4(ZXDB):​c.222G>A​(p.Leu74Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000256 in 1,172,997 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: ZXDB NM_007157.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 1 publications found

Genes affected

ZXDB (HGNC:13199): (zinc finger X-linked duplicated B) The ZXDB gene is one of a pair of duplicated zinc finger genes on chromosome Xp11.21 (Greig et al., 1993 [PubMed 8268913]); see also ZXDA (MIM 300235).[supplied by OMIM, Jul 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=2.17 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007157.4. 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
	ZXDB	NM_007157.4	MANE Select	c.222G>A	p.Leu74Leu	synonymous	Exon 1 of 1	NP_009088.1	P98169

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZXDB	ENST00000374888.3	TSL:6 MANE Select	c.222G>A	p.Leu74Leu	synonymous	Exon 1 of 1	ENSP00000364023.1	P98169

Frequencies

GnomAD3 genomes AF: 0.0000181 AC: 2 AN: 110522 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000381

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.41e-7 AC: 1 AN: 1062475 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 346151

African (AFR) AF: 0.00 AC: 0 AN: 23266

American (AMR) AF: 0.00 AC: 0 AN: 32643

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18313

East Asian (EAS) AF: 0.00 AC: 0 AN: 27011

South Asian (SAS) AF: 0.00 AC: 0 AN: 51105

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33281

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2810

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 829496

Other (OTH) AF: 0.00 AC: 0 AN: 44550

GnomAD4 genome AF: 0.0000181 AC: 2 AN: 110522 Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1 AN XY: 33410

African (AFR) AF: 0.00 AC: 0 AN: 30434

American (AMR) AF: 0.00 AC: 0 AN: 10535

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2592

East Asian (EAS) AF: 0.00 AC: 0 AN: 3430

South Asian (SAS) AF: 0.00 AC: 0 AN: 2695

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6005

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 227

European-Non Finnish (NFE) AF: 0.0000381 AC: 2 AN: 52457

Other (OTH) AF: 0.00 AC: 0 AN: 1480

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.6
DANN	Benign	0.96
PhyloP100		2.2
PromoterAI		0.014	Neutral

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

Other links and lift over

dbSNP: rs768201846; hg19: chrX-57618703;