7-139035682-C-T

Variant names:

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

Variant summary

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

The NM_080660.4(ZC3HAV1L):​c.336G>A​(p.Met112Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000982 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: ZC3HAV1L NM_080660.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 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=0.068581104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1L	NM_080660.4	c.336G>A	p.Met112Ile	missense_variant	Exon 1 of 5	ENST00000275766.2	NP_542391.2
ZC3HAV1L	XM_011516688.4	c.336G>A	p.Met112Ile	missense_variant	Exon 1 of 5		XP_011514990.1
ZC3HAV1L	XM_006716176.4	c.336G>A	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>A	p.Met112Ile	missense_variant	Exon 1 of 5	1	NM_080660.4	ENSP00000275766.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000982 AC: 13 AN: 1324042 Hom.: 0 Cov.: 34 AF XY: 0.0000107 AC XY: 7 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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000114

Gnomad4 OTH exome AF: 0.0000182

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.336G>A (p.M112I) alteration is located in exon 1 (coding exon 1) of the ZC3HAV1L gene. This alteration results from a G to A substitution at nucleotide position 336, causing the methionine (M) at amino acid position 112 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

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	22
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	0.026	D
MetaRNN	Benign	0.069	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		0.096	T
GERP RS		-0.036
Varity_R		0.16
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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;