Genetic Variant ZNG1F:p.Ser82Ile (chr9-41183657-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001085457.2(ZNG1F):c.245G>T(p.Ser82Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000305 in 1,605,298 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000019 ( 4 hom. )

Consequence

ZNG1F
NM_001085457.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91

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 Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.814

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1F	NM_001085457.2 link	c.245G>T	p.Ser82Ile	missense_variant	Exon 3 of 15	ENST00000377391.8	NP_001078926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNG1F	ENST00000377391.8 link	c.245G>T	p.Ser82Ile	missense_variant	Exon 3 of 15	1	NM_001085457.2	ENSP00000366608.4	Q4V339
ZNG1F	ENST00000456520.5 link	c.245G>T	p.Ser82Ile	missense_variant	Exon 3 of 14	1		ENSP00000401079.2	H0Y5V3
ZNG1F	ENST00000382436.7 link	n.113G>T		non_coding_transcript_exon_variant	Exon 3 of 16	1		ENSP00000484049.1	A0A087X1C0
ZNG1F	ENST00000486387.6 link	n.245G>T		non_coding_transcript_exon_variant	Exon 3 of 17	2		ENSP00000480837.1	A0A0B4J2E3

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

149138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000523

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000680

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

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

249784

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1456160

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

724450

show subpopulations

Gnomad4 AFR exome

AF:

0.000751

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000148

AC:

AN:

149138

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

72714

show subpopulations

Gnomad4 AFR

AF:

0.000523

Gnomad4 AMR

AF:

0.0000680

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.000170

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.245G>T (p.S82I) alteration is located in exon 3 (coding exon 3) of the CBWD6 gene. This alteration results from a G to T substitution at nucleotide position 245, causing the serine (S) at amino acid position 82 to be replaced by an isoleucine (I). 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

0.17

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Benign

0.90

DEOGEN2

Benign

0.036

.;T;.;.

LIST_S2

Uncertain

0.86

D;D;D;D

MetaRNN

Pathogenic

0.81

D;D;D;D

Sift4G

Benign

0.38

T;T;T;T

Vest4

0.89

gMVP

0.60

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

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