9-122057-C-T

Variant names:

• chr9-122057-C-T
• rs1398080295
• NM_018491.5:c.985G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018491.5(ZNG1A):​c.985G>A​(p.Val329Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 151,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06874284).

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.985G>A	p.Val329Met	missense	Exon 14 of 15	NP_060961.3
	ZNG1A	NM_001145356.2		c.928G>A	p.Val310Met	missense	Exon 13 of 14	NP_001138828.1	Q9BRT8-3
	ZNG1A	NM_001399807.1		c.925G>A	p.Val309Met	missense	Exon 13 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.985G>A	p.Val329Met	missense	Exon 14 of 15	ENSP00000348915.4	Q9BRT8-1
	ZNG1A	ENST00000377400.8	TSL:1	c.985G>A	p.Val329Met	missense	Exon 14 of 15	ENSP00000366617.5	Q9BRT8-1
	ZNG1A	ENST00000382447.8	TSL:1	c.928G>A	p.Val310Met	missense	Exon 13 of 14	ENSP00000371885.4	Q9BRT8-3

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151546 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000796 AC: 5 AN: 62828 AF XY: 0.0000639

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000620

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: 0.0000295 AC: 43 AN: 1458926 Hom.: 0 Cov.: 31 AF XY: 0.0000262 AC XY: 19 AN XY: 725694

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

African (AFR) AF: 0.0000300 AC: 1 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00103 AC: 41 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111370

Other (OTH) AF: 0.0000166 AC: 1 AN: 60194

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151664 Hom.: 0 Cov.: 30 AF XY: 0.0000270 AC XY: 2 AN XY: 74122

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67704

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000453

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	0.18
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.041
Sift	Benign	0.33	T
Sift4G	Benign	0.45	T
Polyphen		0.14	B
Vest4		0.20
MutPred		0.46		Loss of sheet (P = 0.0817)
MVP		0.13
ClinPred		0.057	T
GERP RS		1.9
Varity_R		0.036
gMVP		0.017
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1398080295; hg19: chr9-122057;