rs1393669125

Variant names:

• chr7-139035682-C-A
• rs1393669125
• NM_080660.4:c.336G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-139035682-C-A
• chr7-139035682-C-G
• chr7-139035682-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080660.4(ZC3HAV1L):​c.336G>T​(p.Met112Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000302 in 1,324,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: ZC3HAV1L NM_080660.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

Genes affected

ZC3HAV1L (HGNC:22423): (zinc finger CCCH-type containing, antiviral 1 like) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060825795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1L	NM_080660.4	c.336G>T	p.Met112Ile	missense_variant	Exon 1 of 5	ENST00000275766.2	NP_542391.2
ZC3HAV1L	XM_011516688.4	c.336G>T	p.Met112Ile	missense_variant	Exon 1 of 5		XP_011514990.1
ZC3HAV1L	XM_006716176.4	c.336G>T	p.Met112Ile	missense_variant	Exon 1 of 4		XP_006716239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3HAV1L	ENST00000275766.2	c.336G>T	p.Met112Ile	missense_variant	Exon 1 of 5	1	NM_080660.4	ENSP00000275766.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000400 AC: 3 AN: 75002 Hom.: 0 AF XY: 0.0000462 AC XY: 2 AN XY: 43250

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: 0.000194

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000302 AC: 4 AN: 1324042 Hom.: 0 Cov.: 34 AF XY: 0.00000613 AC XY: 4 AN XY: 652484

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: 0.0000554

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.50	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.068
Sift	Benign	0.14	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.26		Gain of catalytic residue at M112 (P = 0.1922);
MVP		0.18
MPC		1.6
ClinPred		0.074	T
GERP RS		-0.036
Varity_R		0.16
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1393669125; hg19: chr7-138720428;