9-41133718-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001085457.2(ZNG1F):​c.841G>A​(p.Val281Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 151,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000066 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZNG1F
NM_001085457.2 missense

Scores

7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10
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 -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09296885).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNG1FNM_001085457.2 linkc.841G>A p.Val281Ile missense_variant Exon 12 of 15 ENST00000377391.8 NP_001078926.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNG1FENST00000377391.8 linkc.841G>A p.Val281Ile missense_variant Exon 12 of 15 1 NM_001085457.2 ENSP00000366608.4 Q4V339
ZNG1FENST00000456520.5 linkc.784G>A p.Val262Ile missense_variant Exon 11 of 14 1 ENSP00000401079.2 H0Y5V3
ZNG1FENST00000382436.7 linkn.*386G>A non_coding_transcript_exon_variant Exon 13 of 16 1 ENSP00000484049.1 A0A087X1C0
ZNG1FENST00000486387.6 linkn.*1406G>A non_coding_transcript_exon_variant Exon 14 of 17 2 ENSP00000480837.1 A0A0B4J2E3
ZNG1FENST00000382436.7 linkn.*386G>A 3_prime_UTR_variant Exon 13 of 16 1 ENSP00000484049.1 A0A087X1C0
ZNG1FENST00000486387.6 linkn.*1406G>A 3_prime_UTR_variant Exon 14 of 17 2 ENSP00000480837.1 A0A0B4J2E3

Frequencies

GnomAD3 genomes
AF:
0.000258
AC:
39
AN:
150920
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.000707
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000664
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000984
Gnomad SAS
AF:
0.000211
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000443
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000665
AC:
96
AN:
1444080
Hom.:
0
Cov.:
41
AF XY:
0.0000807
AC XY:
58
AN XY:
718800
show subpopulations
Gnomad4 AFR exome
AF:
0.000330
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000581
Gnomad4 SAS exome
AF:
0.000290
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000279
Gnomad4 OTH exome
AF:
0.0000833
GnomAD4 genome
AF:
0.000258
AC:
39
AN:
151042
Hom.:
0
Cov.:
28
AF XY:
0.000203
AC XY:
15
AN XY:
73790
show subpopulations
Gnomad4 AFR
AF:
0.000705
Gnomad4 AMR
AF:
0.0000663
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000986
Gnomad4 SAS
AF:
0.000211
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000443
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000119
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 16, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.841G>A (p.V281I) alteration is located in exon 12 (coding exon 12) of the CBWD6 gene. This alteration results from a G to A substitution at nucleotide position 841, causing the valine (V) at amino acid position 281 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
0.082
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Benign
0.87
DEOGEN2
Benign
0.00096
.;T;.
LIST_S2
Benign
0.85
D;D;D
MetaRNN
Benign
0.093
T;T;T
Sift4G
Benign
0.39
T;T;T
Vest4
0.20
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
gMVP
0.22

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: rs373196176; hg19: chr9-70912520; API