9-135002-C-T

Variant names:

• chr9-135002-C-T
• rs1410712068
• NM_018491.5:c.793G>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.793G>A​(p.Gly265Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: not found (cov: 20)
  • Exomes 𝑓: 0.0000037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.466
• 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=0.09979612).

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.793G>A	p.Gly265Arg	missense	Exon 11 of 15	NP_060961.3
	ZNG1A	NM_001145356.2		c.736G>A	p.Gly246Arg	missense	Exon 10 of 14	NP_001138828.1	Q9BRT8-3
	ZNG1A	NM_001399807.1		c.733G>A	p.Gly245Arg	missense	Exon 10 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.793G>A	p.Gly265Arg	missense	Exon 11 of 15	ENSP00000348915.4	Q9BRT8-1
	ZNG1A	ENST00000377400.8	TSL:1	c.793G>A	p.Gly265Arg	missense	Exon 11 of 15	ENSP00000366617.5	Q9BRT8-1
	ZNG1A	ENST00000382447.8	TSL:1	c.736G>A	p.Gly246Arg	missense	Exon 10 of 14	ENSP00000371885.4	Q9BRT8-3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.00 AC: 0 AN: 64302 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000374 AC: 5 AN: 1335326 Hom.: 0 Cov.: 21 AF XY: 0.00000602 AC XY: 4 AN XY: 664154

African (AFR) AF: 0.00 AC: 0 AN: 28570

American (AMR) AF: 0.00 AC: 0 AN: 33434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23040

East Asian (EAS) AF: 0.00 AC: 0 AN: 38716

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1028470

Other (OTH) AF: 0.0000722 AC: 4 AN: 55414

GnomAD4 genome Cov.: 20

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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.036	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.47
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.053
Sift	Benign	0.17	T
Sift4G	Benign	0.25	T
Polyphen		0.0090	B
Vest4		0.074
MutPred		0.28		Gain of helix (P = 0.0225)
MVP		0.34
ClinPred		0.098	T
GERP RS		-0.87
Varity_R		0.075
gMVP		0.021
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1410712068; hg19: chr9-135002; COSMIC: COSV100071123;