Genetic Variant ZNG1F:p.Met149Val (chr9-41174338-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001085457.2(ZNG1F):c.445A>G(p.Met149Val) variant causes a missense change. The variant allele was found at a frequency of 0.000147 in 149,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNG1F
NM_001085457.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

ZNG1F (HGNC:31978): (Zn regulated GTPase metalloprotein activator 1F) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNG1F links:

FRG1HP (HGNC:51767): (FSHD region gene 1 family member H, pseudogene)

FRG1HP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1F	NM_001085457.2 link	c.445A>G	p.Met149Val	missense_variant	Exon 5 of 15	ENST00000377391.8	NP_001078926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNG1F	ENST00000377391.8 link	c.445A>G	p.Met149Val	missense_variant	Exon 5 of 15	1	NM_001085457.2	ENSP00000366608.4	Q4V339
ZNG1F	ENST00000456520.5 link	c.445A>G	p.Met149Val	missense_variant	Exon 5 of 14	1		ENSP00000401079.2	H0Y5V3
ZNG1F	ENST00000382436.7 link	n.313A>G		non_coding_transcript_exon_variant	Exon 5 of 16	1		ENSP00000484049.1	A0A087X1C0
ZNG1F	ENST00000467791.5 link	n.34A>G		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000480830.1	A0A087WX94
ZNG1F	ENST00000486387.6 link	n.445A>G		non_coding_transcript_exon_variant	Exon 5 of 17	2		ENSP00000480837.1	A0A0B4J2E3

Frequencies

GnomAD3 genomes

AF:

0.000147

AC:

AN:

149504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000994

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.000222

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000436

AC:

AN:

137716

Hom.:

AF XY:

0.0000653

AC XY:

AN XY:

76626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000843

Gnomad NFE exome

AF:

0.0000327

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000117

AC:

169

AN:

1444980

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

718410

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000351

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000511

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.0000505

GnomAD4 genome

AF:

0.000147

AC:

AN:

149592

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

72920

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.000269

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000994

Gnomad4 NFE

AF:

0.000222

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.445A>G (p.M149V) alteration is located in exon 5 (coding exon 5) of the CBWD6 gene. This alteration results from a A to G substitution at nucleotide position 445, causing the methionine (M) at amino acid position 149 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.015

.;T;.;.

LIST_S2

Uncertain

0.94

D;D;D;D

MetaRNN

Uncertain

0.60

D;D;D;D

PROVEAN

Benign

0.13

.;N;N;.

Sift

Benign

1.0

.;T;D;.

Sift4G

Benign

0.27

T;T;T;T

Vest4

0.73

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over