chrX-57592166-C-T

Variant names:

• chrX-57592166-C-T
• NM_007157.4:c.118C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007157.4(ZXDB):​c.118C>T​(p.Pro40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P40L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ZXDB NM_007157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.259
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14380065).

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.118C>T	p.Pro40Ser	missense	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.118C>T	p.Pro40Ser	missense	Exon 1 of 1	ENSP00000364023.1	P98169

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 937321 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 297013

African (AFR) AF: 0.00 AC: 0 AN: 19231

American (AMR) AF: 0.00 AC: 0 AN: 8095

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12719

East Asian (EAS) AF: 0.00 AC: 0 AN: 21203

South Asian (SAS) AF: 0.00 AC: 0 AN: 33411

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30925

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2425

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 770243

Other (OTH) AF: 0.00 AC: 0 AN: 39069

GnomAD4 genome Cov.: 23

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	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.51
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.26
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.068
Sift	Benign	0.039	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.12	B
Vest4		0.029
MutPred		0.31		Gain of phosphorylation at P40 (P = 0.0203)
MVP		0.14
MPC		1.1
ClinPred		0.22	T
GERP RS		2.4
PromoterAI		0.0060	Neutral
Varity_R		0.030
gMVP		0.082
Mutation Taster		=98/2	polymorphism

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

hg19: chrX-57618599;