Genetic Variant ZNG1F:p.Arg315Lys (chr9-41133512-C-T) – 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.944G>A(p.Arg315Lys) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000039 ( 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: 6.85

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.944G>A	p.Arg315Lys	missense_variant	Exon 13 of 15	ENST00000377391.8	NP_001078926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNG1F	ENST00000377391.8 link	c.944G>A	p.Arg315Lys	missense_variant	Exon 13 of 15	1	NM_001085457.2	ENSP00000366608.4	Q4V339
ZNG1F	ENST00000456520.5 link	c.887G>A	p.Arg296Lys	missense_variant	Exon 12 of 14	1		ENSP00000401079.2	H0Y5V3
ZNG1F	ENST00000382436.7 link	n.*489G>A		non_coding_transcript_exon_variant	Exon 14 of 16	1		ENSP00000484049.1	A0A087X1C0
ZNG1F	ENST00000486387.6 link	n.*1509G>A		non_coding_transcript_exon_variant	Exon 15 of 17	2		ENSP00000480837.1	A0A0B4J2E3
ZNG1F	ENST00000382436.7 link	n.*489G>A		3_prime_UTR_variant	Exon 14 of 16	1		ENSP00000484049.1	A0A087X1C0
ZNG1F	ENST00000486387.6 link	n.*1509G>A		3_prime_UTR_variant	Exon 15 of 17	2		ENSP00000480837.1	A0A0B4J2E3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

94106

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000406

Gnomad ASJ

AF:

0.000733

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000390

AC:

AN:

1281098

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

643666

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000232

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000724

Gnomad4 OTH exome

AF:

0.0000736

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000531

AC:

AN:

94190

Hom.:

Cov.:

AF XY:

0.0000927

AC XY:

AN XY:

43128

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000405

Gnomad4 ASJ

AF:

0.000733

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:

0.0000843

Hom.:

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.944G>A (p.R315K) alteration is located in exon 13 (coding exon 13) of the CBWD6 gene. This alteration results from a G to A substitution at nucleotide position 944, causing the arginine (R) at amino acid position 315 to be replaced by a lysine (K). 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

Pathogenic

0.79

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;T;.

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Uncertain

0.68

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.76

gMVP

0.83

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