Genetic Variant NM_018491.5:c.758G>C (chr9-146108-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_018491.5(ZNG1A):c.758G>C(p.Gly253Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,560,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNG1A
NM_018491.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

Publications

1 publications found

Variant links:

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]

ZNG1A links:

ENSG00000302830 (HGNC:):

ENSG00000302830 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.09464291).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNG1A	NM_018491.5	MANE Select	c.758G>C	p.Gly253Ala	missense	Exon 10 of 15	NP_060961.3
ZNG1A	NM_001399807.1		c.698G>C	p.Gly233Ala	missense	Exon 9 of 14	NP_001386736.1
ZNG1A	NM_001399808.1		c.671G>C	p.Gly224Ala	missense	Exon 9 of 14	NP_001386737.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNG1A	ENST00000356521.9	TSL:1 MANE Select	c.758G>C	p.Gly253Ala	missense	Exon 10 of 15	ENSP00000348915.4	Q9BRT8-1
ZNG1A	ENST00000377400.8	TSL:1	c.758G>C	p.Gly253Ala	missense	Exon 10 of 15	ENSP00000366617.5	Q9BRT8-1
ZNG1A	ENST00000314367.14	TSL:1	c.650G>C	p.Gly217Ala	missense	Exon 11 of 16	ENSP00000323433.10	Q9BRT8-2

Frequencies

GnomAD3 genomes

AF:

0.0000274

AC:

AN:

146208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000793

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:

0.0000800

AC:

AN:

199902

AF XY:

0.0000724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000997

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000996

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1413952

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

703566

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32284

American (AMR)

AF:

0.00

AC:

AN:

40414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25344

East Asian (EAS)

AF:

0.000562

AC:

AN:

39160

South Asian (SAS)

AF:

0.00

AC:

AN:

80720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4006

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1094508

Other (OTH)

AF:

0.0000170

AC:

AN:

58796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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

AF:

0.0000274

AC:

AN:

146208

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70900

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39608

American (AMR)

AF:

0.00

AC:

AN:

14244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3362

East Asian (EAS)

AF:

0.000793

AC:

AN:

5042

South Asian (SAS)

AF:

0.00

AC:

AN:

4360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66592

Other (OTH)

AF:

0.00

AC:

AN:

1972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000849

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.016

Eigen

Benign

-0.060

Eigen_PC

Benign

-0.023

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.012

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

PhyloP100

3.9

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Benign

0.14

Sift4G

Benign

0.75

Polyphen

0.76

Vest4

0.58

MutPred

0.36

Gain of helix (P = 0.0854)

MVP

0.59

ClinPred

0.12

GERP RS

3.4

PromoterAI

0.0013

Neutral

(source)

Varity_R

0.19

gMVP

0.025

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over