9-123412-C-T

Variant names:

• chr9-123412-C-T
• rs1405584714
• NM_018491.5:c.859G>A

Variant summary

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

The NM_018491.5(ZNG1A):​c.859G>A​(p.Glu287Lys) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1A	NM_018491.5	c.859G>A	p.Glu287Lys	missense_variant	Exon 12 of 15	ENST00000356521.9	NP_060961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNG1A	ENST00000356521.9	c.859G>A	p.Glu287Lys	missense_variant	Exon 12 of 15	1	NM_018491.5	ENSP00000348915.4
ZNG1A	ENST00000465014.6	n.*457G>A		non_coding_transcript_exon_variant	Exon 12 of 15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*580G>A		non_coding_transcript_exon_variant	Exon 13 of 16	1		ENSP00000477749.1
ZNG1A	ENST00000616944.4	n.*404G>A		non_coding_transcript_exon_variant	Exon 13 of 14	2		ENSP00000482821.1
ZNG1A	ENST00000619157.4	n.*404G>A		non_coding_transcript_exon_variant	Exon 9 of 12	5		ENSP00000483746.1
ZNG1A	ENST00000465014.6	n.*457G>A		3_prime_UTR_variant	Exon 12 of 15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*580G>A		3_prime_UTR_variant	Exon 13 of 16	1		ENSP00000477749.1
ZNG1A	ENST00000616944.4	n.*404G>A		3_prime_UTR_variant	Exon 13 of 14	2		ENSP00000482821.1
ZNG1A	ENST00000619157.4	n.*404G>A		3_prime_UTR_variant	Exon 9 of 12	5		ENSP00000483746.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 150606 Hom.: 0 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000454 AC: 6 AN: 1322362 Hom.: 0 Cov.: 23 AF XY: 0.00000755 AC XY: 5 AN XY: 662638

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000797

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: 0.00000295

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000133 AC: 2 AN: 150606 Hom.: 0 Cov.: 25 AF XY: 0.0000272 AC XY: 2 AN XY: 73416

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000662

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.859G>A (p.E287K) alteration is located in exon 12 (coding exon 12) of the CBWD1 gene. This alteration results from a G to A substitution at nucleotide position 859, causing the glutamic acid (E) at amino acid position 287 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	Benign	0.16
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T;T;.;T;.
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	.;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.61	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.98	N;.;N;.;N
REVEL	Benign	0.22
Sift	Benign	0.26	T;.;T;.;T
Sift4G	Benign	0.64	T;T;T;T;T
Polyphen		0.12	B;B;B;.;B
Vest4		0.63
MutPred		0.51		Gain of helix (P = 0.0093);Gain of helix (P = 0.0093);.;.;.;
MVP		0.75
ClinPred		0.24	T
GERP RS		3.2
Varity_R		0.36
gMVP		0.041

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: rs1405584714; hg19: chr9-123412;