9-146108-C-T

Variant names:

• chr9-146108-C-T
• rs747982019
• NM_018491.5:c.758G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018491.5(ZNG1A):​c.758G>A​(p.Gly253Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G253A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.758G>A	p.Gly253Glu	missense	Exon 10 of 15	NP_060961.3
	ZNG1A	NM_001399807.1		c.698G>A	p.Gly233Glu	missense	Exon 9 of 14	NP_001386736.1
	ZNG1A	NM_001399808.1		c.671G>A	p.Gly224Glu	missense	Exon 9 of 14	NP_001386737.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNG1A	ENST00000356521.9	TSL:1 MANE Select	c.758G>A	p.Gly253Glu	missense	Exon 10 of 15	ENSP00000348915.4	Q9BRT8-1
	ZNG1A	ENST00000377400.8	TSL:1	c.758G>A	p.Gly253Glu	missense	Exon 10 of 15	ENSP00000366617.5	Q9BRT8-1
	ZNG1A	ENST00000314367.14	TSL:1	c.650G>A	p.Gly217Glu	missense	Exon 11 of 16	ENSP00000323433.10	Q9BRT8-2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.07e-7 AC: 1 AN: 1413952 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 703566

African (AFR) AF: 0.00 AC: 0 AN: 32284

American (AMR) AF: 0.00 AC: 0 AN: 40414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25344

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39160

South Asian (SAS) AF: 0.00 AC: 0 AN: 80720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4006

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094508

Other (OTH) AF: 0.00 AC: 0 AN: 58796

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.031
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.35	T
Sift4G	Benign	0.90	T
Polyphen		0.96	P
Vest4		0.75
MutPred		0.41		Gain of helix (P = 0.027)
MVP		0.60
ClinPred		0.70	D
GERP RS		3.4
PromoterAI		0.0020	Neutral
Varity_R		0.18
gMVP		0.030
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs747982019; hg19: chr9-146108;