X-152915166-A-G

Position:

• chrX-152915166-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395254.1(ZNF185):​c.187A>G​(p.Thr63Ala) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF185 NM_001395254.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

Genes affected

ZNF185 (HGNC:12976): (zinc finger protein 185 with LIM domain) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a LIM-domain zinc finger protein. The LIM domain is composed of two contiguous zinc finger domains, separated by a two-amino acid residue hydrophobic linker. The LIM domain mediates protein:protein interactions. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17663419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF185	NM_001395254.1	c.187A>G	p.Thr63Ala	missense_variant	4/25	ENST00000695776.1	NP_001382183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF185	ENST00000695776.1	c.187A>G	p.Thr63Ala	missense_variant	4/25		NM_001395254.1	ENSP00000512166.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.187A>G (p.T63A) alteration is located in exon 3 (coding exon 3) of the ZNF185 gene. This alteration results from a A to G substitution at nucleotide position 187, causing the threonine (T) at amino acid position 63 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	.;.;.;.;T;.
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.60	T;T;T;T;T;.
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L;L;L;L;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.0	N;N;N;N;N;.
REVEL	Benign	0.032
Sift	Uncertain	0.0060	D;D;D;D;D;.
Sift4G	Benign	0.082	T;T;T;T;T;T
Polyphen		0.59, 0.23	.;P;.;.;B;.
Vest4		0.43
MutPred		0.19		Loss of phosphorylation at T63 (P = 0.0193);Loss of phosphorylation at T63 (P = 0.0193);Loss of phosphorylation at T63 (P = 0.0193);Loss of phosphorylation at T63 (P = 0.0193);Loss of phosphorylation at T63 (P = 0.0193);Loss of phosphorylation at T63 (P = 0.0193);
MVP		0.048
MPC		0.12
ClinPred		0.54	D
GERP RS		3.9
Varity_R		0.13
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152083710;