9-121526-C-T

Position:

• chr9-121526-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018491.5(ZNG1A):​c.1129G>A​(p.Val377Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.301811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5	c.1129G>A	p.Val377Met	missense_variant	15/15	ENST00000356521.9	NP_060961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNG1A	ENST00000356521.9	c.1129G>A	p.Val377Met	missense_variant	15/15	1	NM_018491.5	ENSP00000348915.4
ZNG1A	ENST00000465014.6	n.*727G>A		non_coding_transcript_exon_variant	15/15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*850G>A		non_coding_transcript_exon_variant	16/16	1		ENSP00000477749.1
ZNG1A	ENST00000619157.4	n.*674G>A		non_coding_transcript_exon_variant	12/12	5		ENSP00000483746.1
ZNG1A	ENST00000465014.6	n.*727G>A		3_prime_UTR_variant	15/15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*850G>A		3_prime_UTR_variant	16/16	1		ENSP00000477749.1
ZNG1A	ENST00000619157.4	n.*674G>A		3_prime_UTR_variant	12/12	5		ENSP00000483746.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.1129G>A (p.V377M) alteration is located in exon 15 (coding exon 15) of the CBWD1 gene. This alteration results from a G to A substitution at nucleotide position 1129, causing the valine (V) at amino acid position 377 to be replaced by a methionine (M). 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	0.21
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0090	T;T;.;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	.;D;D;D;D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.30	T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.80	N;.;N;.;N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;.;D;.;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		1.0	D;D;D;.;D
Vest4		0.29
MVP		0.42
ClinPred		0.85	D
GERP RS		3.1
Varity_R		0.11
gMVP		0.018

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

Other links and lift over

dbSNP: rs374210854; hg19: chr9-121526;