9-41183657-C-A

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

1
1
5

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

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
ZNG1FNM_001085457.2 linkc.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 Appris UniProt
ZNG1FENST00000377391.8 linkc.245G>T p.Ser82Ile missense_variant Exon 3 of 15 1 NM_001085457.2 ENSP00000366608.4 Q4V339
ZNG1FENST00000456520.5 linkc.245G>T p.Ser82Ile missense_variant Exon 3 of 14 1 ENSP00000401079.2 H0Y5V3
ZNG1FENST00000382436.7 linkn.113G>T non_coding_transcript_exon_variant Exon 3 of 16 1 ENSP00000484049.1 A0A087X1C0
ZNG1FENST00000486387.6 linkn.245G>T non_coding_transcript_exon_variant Exon 3 of 17 2 ENSP00000480837.1 A0A0B4J2E3

Frequencies

GnomAD3 genomes
AF:
0.000148
AC:
22
AN:
149138
Hom.:
0
Cov.:
27
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:
12
AN:
249784
Hom.:
1
AF XY:
0.0000592
AC XY:
8
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:
27
AN:
1456160
Hom.:
4
Cov.:
34
AF XY:
0.0000179
AC XY:
13
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:
22
AN:
149138
Hom.:
0
Cov.:
27
AF XY:
0.000138
AC XY:
10
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.:
0
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
24
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.

Other links and lift over

dbSNP: rs748958590; hg19: chr9-70862532; API