9-154770-G-C

Position:

chr9-154770-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018491.5(ZNG1A):c.601C>G(p.Leu201Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,594,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ZNG1A
NM_018491.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

ZNG1A (HGNC:17134): (Zn regulated GTPase metalloprotein activator 1A) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNG1A links:

ZNG1A (HGNC:):

ZNG1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1468432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5 linkuse as main transcript	c.601C>G	p.Leu201Val	missense_variant	8/15	ENST00000356521.9	NP_060961.3	Q9BRT8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNG1A	ENST00000356521.9 linkuse as main transcript	c.601C>G	p.Leu201Val	missense_variant	8/15	1	NM_018491.5	ENSP00000348915.4	Q9BRT8-1
ZNG1A	ENST00000616803.4 linkuse as main transcript	n.*240C>G		non_coding_transcript_exon_variant	7/8	5		ENSP00000479698.1	A0A087WVU7
ZNG1A	ENST00000616944.4 linkuse as main transcript	n.*146C>G		non_coding_transcript_exon_variant	9/14	2		ENSP00000482821.1	A0A087WZQ3
ZNG1A	ENST00000618361.4 linkuse as main transcript	n.*146C>G		non_coding_transcript_exon_variant	5/8	5		ENSP00000480295.1	A0A087WWK6
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*146C>G		non_coding_transcript_exon_variant	5/12	5		ENSP00000483746.1	A0A087X0Y9
ZNG1A	ENST00000616803.4 linkuse as main transcript	n.*240C>G		3_prime_UTR_variant	7/8	5		ENSP00000479698.1	A0A087WVU7
ZNG1A	ENST00000616944.4 linkuse as main transcript	n.*146C>G		3_prime_UTR_variant	9/14	2		ENSP00000482821.1	A0A087WZQ3
ZNG1A	ENST00000618361.4 linkuse as main transcript	n.*146C>G		3_prime_UTR_variant	5/8	5		ENSP00000480295.1	A0A087WWK6
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*146C>G		3_prime_UTR_variant	5/12	5		ENSP00000483746.1	A0A087X0Y9
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*120+1711C>G		intron_variant		2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*260+1711C>G		intron_variant		1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000618061.4 linkuse as main transcript	n.*120+1711C>G		intron_variant		1		ENSP00000477647.1	A0A087WWK6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000256

AC:

AN:

234748

Hom.:

AF XY:

0.00000783

AC XY:

AN XY:

127762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000120

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:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000284

AC:

AN:

1442656

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

718134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000910

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:

0.0000334

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.601C>G (p.L201V) alteration is located in exon 8 (coding exon 8) of the CBWD1 gene. This alteration results from a C to G substitution at nucleotide position 601, causing the leucine (L) at amino acid position 201 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0086

T;T;.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.97

.;D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

N;N;.;N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.21

N;N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.39

T;T;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T

Polyphen

0.020

B;B;B;B;.

Vest4

0.35

MutPred

0.49

Gain of catalytic residue at L201 (P = 0.0634);Gain of catalytic residue at L201 (P = 0.0634);.;Gain of catalytic residue at L201 (P = 0.0634);Gain of catalytic residue at L201 (P = 0.0634);

MVP

0.36

ClinPred

0.044

GERP RS

2.3

Varity_R

0.067

gMVP

0.019

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