9-135002-C-T

Position:

• chr9-135002-C-T

Variant summary

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

The NM_018491.5(ZNG1A):​c.793G>A​(p.Gly265Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: not found (cov: 20)
  • Exomes 𝑓: 0.0000037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.466

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09979612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5	c.793G>A	p.Gly265Arg	missense_variant	11/15	ENST00000356521.9	NP_060961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNG1A	ENST00000356521.9	c.793G>A	p.Gly265Arg	missense_variant	11/15	1	NM_018491.5	ENSP00000348915.4
ZNG1A	ENST00000465014.6	n.*391G>A		non_coding_transcript_exon_variant	11/15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*514G>A		non_coding_transcript_exon_variant	12/16	1		ENSP00000477749.1
ZNG1A	ENST00000616944.4	n.*338G>A		non_coding_transcript_exon_variant	12/14	2		ENSP00000482821.1
ZNG1A	ENST00000619157.4	n.*338G>A		non_coding_transcript_exon_variant	8/12	5		ENSP00000483746.1
ZNG1A	ENST00000465014.6	n.*391G>A		3_prime_UTR_variant	11/15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*514G>A		3_prime_UTR_variant	12/16	1		ENSP00000477749.1
ZNG1A	ENST00000616944.4	n.*338G>A		3_prime_UTR_variant	12/14	2		ENSP00000482821.1
ZNG1A	ENST00000619157.4	n.*338G>A		3_prime_UTR_variant	8/12	5		ENSP00000483746.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000374 AC: 5 AN: 1335326 Hom.: 0 Cov.: 21 AF XY: 0.00000602 AC XY: 4 AN XY: 664154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000722

GnomAD4 genome Cov.: 20

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

Jul 30, 2023

The c.793G>A (p.G265R) alteration is located in exon 11 (coding exon 11) of the CBWD1 gene. This alteration results from a G to A substitution at nucleotide position 793, causing the glycine (G) at amino acid position 265 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.0046	T;T;.;T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.036	N
LIST_S2	Uncertain	0.95	.;D;D;D;D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;N;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.32	N;.;N;.;N
REVEL	Benign	0.053
Sift	Benign	0.17	T;.;T;.;T
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.0090	B;B;B;.;B
Vest4		0.074
MutPred		0.28		Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);.;.;.;
MVP		0.34
ClinPred		0.098	T
GERP RS		-0.87
Varity_R		0.075
gMVP		0.021

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1410712068; hg19: chr9-135002; COSMIC: COSV100071123;