X-135349149-G-A

Position:

• chrX-135349149-G-A

Variant summary

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

The NM_152695.6(ZNF449):​c.394G>A​(p.Val132Met) 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 (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF449 NM_152695.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.30

Genes affected

ZNF449 (HGNC:21039): (zinc finger protein 449) This gene encodes a nuclear protein that likely functions as a transcription factor. The protein includes an N-terminal SCAN domain, and seven C2H2-type zinc finger motifs. [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=0.108394444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF449	NM_152695.6	c.394G>A	p.Val132Met	missense_variant	3/5	ENST00000339249.5	NP_689908.3
ZNF449	XM_047441914.1	c.394G>A	p.Val132Met	missense_variant	3/5		XP_047297870.1
ZNF449	XM_017029351.2	c.49G>A	p.Val17Met	missense_variant	4/6		XP_016884840.1
ZNF449	XM_047441915.1	c.49G>A	p.Val17Met	missense_variant	4/6		XP_047297871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF449	ENST00000339249.5	c.394G>A	p.Val132Met	missense_variant	3/5	1	NM_152695.6	ENSP00000339585.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Short stature Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Nov 18, 2001

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.097	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.074
Sift	Benign	0.081	T
Sift4G	Benign	0.087	T
Polyphen		0.062	B
Vest4		0.20
MutPred		0.57		Gain of disorder (P = 0.0421);
MVP		0.38
MPC		1.6
ClinPred		0.14	T
GERP RS		1.8
Varity_R		0.073
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: rs1569497334; hg19: chrX-134483074;