9-123412-C-T

Variant names:

• chr9-123412-C-T
• rs1405584714
• NM_018491.5:c.859G>A

Variant summary

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

The NM_018491.5(ZNG1A):​c.859G>A​(p.Glu287Lys) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89
• 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 0 ACMG points.

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.859G>A	p.Glu287Lys	missense	Exon 12 of 15	NP_060961.3
	ZNG1A	NM_001145356.2		c.802G>A	p.Glu268Lys	missense	Exon 11 of 14	NP_001138828.1	Q9BRT8-3
	ZNG1A	NM_001399807.1		c.799G>A	p.Glu267Lys	missense	Exon 11 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.859G>A	p.Glu287Lys	missense	Exon 12 of 15	ENSP00000348915.4	Q9BRT8-1
	ZNG1A	ENST00000377400.8	TSL:1	c.859G>A	p.Glu287Lys	missense	Exon 12 of 15	ENSP00000366617.5	Q9BRT8-1
	ZNG1A	ENST00000382447.8	TSL:1	c.802G>A	p.Glu268Lys	missense	Exon 11 of 14	ENSP00000371885.4	Q9BRT8-3

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150606 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000330 AC: 1 AN: 30308 AF XY: 0.0000640

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000454 AC: 6 AN: 1322362 Hom.: 0 Cov.: 23 AF XY: 0.00000755 AC XY: 5 AN XY: 662638

African (AFR) AF: 0.00 AC: 0 AN: 30162

American (AMR) AF: 0.0000797 AC: 3 AN: 37628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23352

East Asian (EAS) AF: 0.00 AC: 0 AN: 39276

South Asian (SAS) AF: 0.00 AC: 0 AN: 78532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3764

European-Non Finnish (NFE) AF: 0.00000295 AC: 3 AN: 1015954

Other (OTH) AF: 0.00 AC: 0 AN: 55662

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000133 AC: 2 AN: 150606 Hom.: 0 Cov.: 25 AF XY: 0.0000272 AC XY: 2 AN XY: 73416

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41046

American (AMR) AF: 0.0000662 AC: 1 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67416

Other (OTH) AF: 0.00 AC: 0 AN: 2058

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.16
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.22
Sift	Benign	0.26	T
Sift4G	Benign	0.64	T
Polyphen		0.12	B
Vest4		0.63
MutPred		0.51		Gain of helix (P = 0.0093)
MVP		0.75
ClinPred		0.24	T
GERP RS		3.2
Varity_R		0.36
gMVP		0.041
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: rs1405584714; hg19: chr9-123412;