chr9-122034-C-G

Variant names:

• chr9-122034-C-G
• rs1587387224
• NM_018491.5:c.1008G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018491.5(ZNG1A):​c.1008G>C​(p.Glu336Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.209
• Publications: 0 publications found

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]

ENSG00000302830 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2502619).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018491.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNG1A	NM_018491.5	MANE Select	c.1008G>C	p.Glu336Asp	missense	Exon 14 of 15	NP_060961.3
	ZNG1A	NM_001145356.2		c.951G>C	p.Glu317Asp	missense	Exon 13 of 14	NP_001138828.1	Q9BRT8-3
	ZNG1A	NM_001399807.1		c.948G>C	p.Glu316Asp	missense	Exon 13 of 14	NP_001386736.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNG1A	ENST00000356521.9	TSL:1 MANE Select	c.1008G>C	p.Glu336Asp	missense	Exon 14 of 15	ENSP00000348915.4	Q9BRT8-1
	ZNG1A	ENST00000377400.8	TSL:1	c.1008G>C	p.Glu336Asp	missense	Exon 14 of 15	ENSP00000366617.5	Q9BRT8-1
	ZNG1A	ENST00000382447.8	TSL:1	c.951G>C	p.Glu317Asp	missense	Exon 13 of 14	ENSP00000371885.4	Q9BRT8-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.21
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.10
Sift	Benign	0.28	T
Sift4G	Benign	0.48	T
Polyphen		0.74	P
Vest4		0.40
MutPred		0.64		Loss of sheet (P = 0.0817)
MVP		0.34
ClinPred		0.77	D
GERP RS		2.0
Varity_R		0.20
gMVP		0.020
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1587387224; hg19: chr9-122034;