9-122090-C-T

Variant names:

• chr9-122090-C-T
• rs878873072
• NM_018491.5:c.952G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_018491.5(ZNG1A):​c.952G>A​(p.Gly318Arg) variant causes a missense, splice region change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense, splice_region
• Scores: Splicing: ADA: 0.9909
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.24

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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1A	NM_018491.5	c.952G>A	p.Gly318Arg	missense_variant, splice_region_variant	Exon 14 of 15	ENST00000356521.9	NP_060961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNG1A	ENST00000356521.9	c.952G>A	p.Gly318Arg	missense_variant, splice_region_variant	Exon 14 of 15	1	NM_018491.5	ENSP00000348915.4
ZNG1A	ENST00000465014.6	n.*550G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 14 of 15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*673G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 15 of 16	1		ENSP00000477749.1
ZNG1A	ENST00000619157.4	n.*497G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 11 of 12	5		ENSP00000483746.1
ZNG1A	ENST00000465014.6	n.*550G>A		3_prime_UTR_variant	Exon 14 of 15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*673G>A		3_prime_UTR_variant	Exon 15 of 16	1		ENSP00000477749.1
ZNG1A	ENST00000619157.4	n.*497G>A		3_prime_UTR_variant	Exon 11 of 12	5		ENSP00000483746.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3 AN: 151090 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000631

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000802 AC: 5 AN: 62354 Hom.: 0 AF XY: 0.0000645 AC XY: 2 AN XY: 31028

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000796

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000288 AC: 42 AN: 1457856 Hom.: 0 Cov.: 31 AF XY: 0.0000414 AC XY: 30 AN XY: 724922

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: 0.000453

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000499

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000199 AC: 3 AN: 151090 Hom.: 0 Cov.: 30 AF XY: 0.0000407 AC XY: 3 AN XY: 73740

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000631

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

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

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.952G>A (p.G318R) alteration is located in exon 14 (coding exon 14) of the CBWD1 gene. This alteration results from a G to A substitution at nucleotide position 952, causing the glycine (G) at amino acid position 318 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;.;T;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Pathogenic	3.9	H;H;.;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.6	D;.;D;.;D
REVEL	Pathogenic	0.87
Sift	Pathogenic	0.0	D;.;D;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		1.0	D;D;D;.;D
Vest4		0.96
MutPred		0.86		Gain of MoRF binding (P = 0.0121);Gain of MoRF binding (P = 0.0121);.;.;.;
MVP		0.92
ClinPred		0.99	D
GERP RS		2.9
Varity_R		0.92
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: 46

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878873072; hg19: chr9-122090;