rs374210854

Variant names:

• chr9-121526-C-G
• rs374210854
• NM_018491.5:c.1129G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-121526-C-G
• chr9-121526-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018491.5(ZNG1A):​c.1129G>C​(p.Val377Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V377M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: ZNG1A NM_018491.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21593824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1A	NM_018491.5	c.1129G>C	p.Val377Leu	missense_variant	Exon 15 of 15	ENST00000356521.9	NP_060961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNG1A	ENST00000356521.9	c.1129G>C	p.Val377Leu	missense_variant	Exon 15 of 15	1	NM_018491.5	ENSP00000348915.4
ZNG1A	ENST00000465014.6	n.*727G>C		non_coding_transcript_exon_variant	Exon 15 of 15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*850G>C		non_coding_transcript_exon_variant	Exon 16 of 16	1		ENSP00000477749.1
ZNG1A	ENST00000619157.4	n.*674G>C		non_coding_transcript_exon_variant	Exon 12 of 12	5		ENSP00000483746.1
ZNG1A	ENST00000465014.6	n.*727G>C		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000482298.1
ZNG1A	ENST00000612045.4	n.*850G>C		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000477749.1
ZNG1A	ENST00000619157.4	n.*674G>C		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000483746.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152118 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152118 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74298

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0025	T;T;.;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	.;D;D;D;D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.26	N;.;N;.;N
REVEL	Benign	0.17
Sift	Benign	0.26	T;.;T;.;T
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.24	B;B;B;.;B
Vest4		0.26
MutPred		0.55		Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);.;.;.;
MVP		0.56
ClinPred		0.75	D
GERP RS		3.1
Varity_R		0.071
gMVP		0.016

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: rs374210854; hg19: chr9-121526;