Genetic Variant ZNG1C:p.Asp350Glu (chr9-68299062-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_201453.4(ZNG1C):c.1050C>A(p.Asp350Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNG1C
NM_201453.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.366

Publications

0 publications found

Variant links:

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]

ZNG1C links:

ENSG00000300460 (HGNC:):

ENSG00000300460 links:

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ACMG classification

Classification was made for transcript

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=0.053082317).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNG1C	NM_201453.4	MANE Select	c.1050C>A	p.Asp350Glu	missense	Exon 14 of 15	NP_958861.2	Q5JTY5-1
ZNG1C	NM_001291821.2		c.990C>A	p.Asp330Glu	missense	Exon 13 of 14	NP_001278750.1	Q5JTY5-2
ZNG1C	NM_001378113.1		c.981C>A	p.Asp327Glu	missense	Exon 13 of 14	NP_001365042.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000756

AC:

AN:

132314

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000985

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:

6.86e-7

AC:

AN:

1458742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725632

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111496

Other (OTH)

AF:

0.00

AC:

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000854

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.72

M_CAP

Benign

0.0036

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.91

PhyloP100

0.37

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.95

REVEL

Benign

0.051

Sift

Benign

0.21

Sift4G

Benign

0.52

Polyphen

0.0040

Vest4

0.078

MutPred

0.51

Gain of sheet (P = 0.0061)

MVP

0.14

MPC

1.3

ClinPred

0.093

GERP RS

-0.23

Varity_R

0.070

gMVP

0.15

Mutation Taster

=82/18

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over