9-68247661-A-G

Position:

• chr9-68247661-A-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_201453.4(ZNG1C):​c.290A>G​(p.Tyr97Cys) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000074 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNG1C NM_201453.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.22

Genes affected

ZNG1C (HGNC:18519): (Zn regulated GTPase metalloprotein activator 1C) 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.402843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNG1C	NM_201453.4	c.290A>G	p.Tyr97Cys	missense_variant	3/15	ENST00000360171.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNG1C	ENST00000360171.11	c.290A>G	p.Tyr97Cys	missense_variant	3/15	1	NM_201453.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 135804 Hom.: 0 Cov.: 20 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000158

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000964 AC: 1 AN: 103752 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52600

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000498 AC: 6 AN: 1205626 Hom.: 0 Cov.: 16 AF XY: 0.00000663 AC XY: 4 AN XY: 603156

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: 0.0000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000440

Gnomad4 OTH exome AF: 0.0000194

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000736 AC: 1 AN: 135804 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 65244

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000158

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.060	T;.;.;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;.;D;D;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.40	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.5	D;.;.;D;.
REVEL	Benign	0.27
Sift	Benign	0.061	T;.;.;T;.
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		0.037	B;.;.;.;.
Vest4		0.67
MutPred		0.52		Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);
MVP		0.31
MPC		2.2
ClinPred		0.68	D
GERP RS		3.5
Varity_R		0.69
gMVP		0.67

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: rs1485821130; hg19: chr9-70862577;