rs782289490

Variant names:

• chr9-68299062-C-G
• rs782289490
• NM_201453.4:c.1050C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-68299062-C-G
• chr9-68299062-C-A
• chr9-68299062-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201453.4(ZNG1C):​c.1050C>G​(p.Asp350Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,422 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 0.0000066 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0000075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1C NM_201453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.366
• Publications: 0 publications found

Genes affected

ZNG1C (HGNC:18519): (Zn regulated GTPase metalloprotein activator 1C) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000300460 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019752324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201453.4. 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
	ZNG1C	NM_201453.4	MANE Select	c.1050C>G	p.Asp350Glu	missense	Exon 14 of 15	NP_958861.2	Q5JTY5-1
	ZNG1C	NM_001291821.2		c.990C>G	p.Asp330Glu	missense	Exon 13 of 14	NP_001278750.1	Q5JTY5-2
	ZNG1C	NM_001378113.1		c.981C>G	p.Asp327Glu	missense	Exon 13 of 14	NP_001365042.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNG1C	ENST00000360171.11	TSL:1 MANE Select	c.1050C>G	p.Asp350Glu	missense	Exon 14 of 15	ENSP00000353295.6	Q5JTY5-1
	ZNG1C	ENST00000377342.9	TSL:1	c.993C>G	p.Asp331Glu	missense	Exon 13 of 14	ENSP00000366559.6	A0A0A0MRU4
	ZNG1C	ENST00000618217.4	TSL:1	c.906C>G	p.Asp302Glu	missense	Exon 12 of 13	ENSP00000480203.1	A0A087WWG3

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151422 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000378 AC: 5 AN: 132314 AF XY: 0.0000572

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000188

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000330

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000754 AC: 11 AN: 1458748 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 725634

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

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.000112 AC: 5 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 85978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111502

Other (OTH) AF: 0.00 AC: 0 AN: 60162

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000970254), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151422 Hom.: 0 Cov.: 21 AF XY: 0.0000135 AC XY: 1 AN XY: 73888

African (AFR) AF: 0.00 AC: 0 AN: 41178

American (AMR) AF: 0.0000658 AC: 1 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67796

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000256 AC: 3

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	0.11
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L
PhyloP100		0.37
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.051
Sift	Benign	0.21	T
Sift4G	Benign	0.52	T
Polyphen		0.0040	B
Vest4		0.078
MutPred		0.51		Gain of sheet (P = 0.0061)
MVP		0.14
MPC		1.3
ClinPred		0.035	T
GERP RS		-0.23
Varity_R		0.070
gMVP		0.15
Mutation Taster		=82/18	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: rs782289490; hg19: chr9-70913978;