9-123380-A-G

Position:

• chr9-123380-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000356521.9(ZNG1A):​c.885+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 25)
  • Exomes 𝑓: 0.0019 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A ENST00000356521.9 splice_donor_region, intron
• Scores: Splicing: ADA: 0.003077
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.568

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-123380-A-G is Benign according to our data. Variant chr9-123380-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2673164.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5	c.885+6T>C		splice_donor_region_variant, intron_variant		ENST00000356521.9	NP_060961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNG1A	ENST00000356521.9	c.885+6T>C		splice_donor_region_variant, intron_variant		1	NM_018491.5	ENSP00000348915	P1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 224 AN: 150942 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.000388

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000330

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00276

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.000484

GnomAD3 exomes AF: 0.00211 AC: 70 AN: 33162 Hom.: 10 AF XY: 0.00182 AC XY: 31 AN XY: 16992

Gnomad AFR exome AF: 0.000786

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.00403

Gnomad OTH exome AF: 0.00192

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00192 AC: 2756 AN: 1438376 Hom.: 2 Cov.: 29 AF XY: 0.00179 AC XY: 1278 AN XY: 715794

Gnomad4 AFR exome AF: 0.000391

Gnomad4 AMR exome AF: 0.000450

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000199

Gnomad4 FIN exome AF: 0.00387

Gnomad4 NFE exome AF: 0.00223

Gnomad4 OTH exome AF: 0.00140

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00148 AC: 224 AN: 151054 Hom.: 1 Cov.: 25 AF XY: 0.00151 AC XY: 111 AN XY: 73730

Gnomad4 AFR AF: 0.000387

Gnomad4 AMR AF: 0.000329

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00276

Gnomad4 NFE AF: 0.00257

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.00124

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

ZNG1A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0031
dbscSNV1_RF	Benign	0.080
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: rs199967278; hg19: chr9-123380;