NM_018491.5:c.1129G>A

Variant names:

• chr9-121526-C-T
• rs374210854
• NM_018491.5:c.1129G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018491.5(ZNG1A):​c.1129G>A​(p.Val377Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82
• Publications: 1 publications found

Genes affected

ZNG1A (HGNC:17134): (Zn regulated GTPase metalloprotein activator 1A) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302830 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.301811).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018491.5. 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
	ZNG1A	NM_018491.5	MANE Select	c.1129G>A	p.Val377Met	missense	Exon 15 of 15	NP_060961.3
	ZNG1A	NM_001145356.2		c.1072G>A	p.Val358Met	missense	Exon 14 of 14	NP_001138828.1	Q9BRT8-3
	ZNG1A	NM_001399807.1		c.1069G>A	p.Val357Met	missense	Exon 14 of 14	NP_001386736.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNG1A	ENST00000356521.9	TSL:1 MANE Select	c.1129G>A	p.Val377Met	missense	Exon 15 of 15	ENSP00000348915.4	Q9BRT8-1
	ZNG1A	ENST00000377400.8	TSL:1	c.1129G>A	p.Val377Met	missense	Exon 15 of 15	ENSP00000366617.5	Q9BRT8-1
	ZNG1A	ENST00000382447.8	TSL:1	c.1072G>A	p.Val358Met	missense	Exon 14 of 14	ENSP00000371885.4	Q9BRT8-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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	0.21
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0090	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.29
MVP		0.42
ClinPred		0.85	D
GERP RS		3.1
Varity_R		0.11
gMVP		0.018
Mutation Taster		=83/17	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

dbSNP: rs374210854; hg19: chr9-121526;