7-139035729-C-T

Variant names:

• chr7-139035729-C-T
• rs935154773
• NM_080660.4:c.289G>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.289G>A​(p.Gly97Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,335,720 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: 7.5e-7 (0 hom.)
• Consequence: ZC3HAV1L NM_080660.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.67

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=0.075014085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1L	NM_080660.4	c.289G>A	p.Gly97Ser	missense_variant	Exon 1 of 5	ENST00000275766.2	NP_542391.2
ZC3HAV1L	XM_011516688.4	c.289G>A	p.Gly97Ser	missense_variant	Exon 1 of 5		XP_011514990.1
ZC3HAV1L	XM_006716176.4	c.289G>A	p.Gly97Ser	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.289G>A	p.Gly97Ser	missense_variant	Exon 1 of 5	1	NM_080660.4	ENSP00000275766.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1335720 Hom.: 0 Cov.: 34 AF XY: 0.00000152 AC XY: 1 AN XY: 658540

Gnomad4 AFR exome AF: 0.0000371

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.289G>A (p.G97S) 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 289, causing the glycine (G) at amino acid position 97 to be replaced by a serine (S). 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	Benign	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.034
Sift	Benign	0.51	T
Sift4G	Benign	0.19	T
Polyphen		0.78	P
Vest4		0.18
MutPred		0.29		Gain of loop (P = 0.069);
MVP		0.061
MPC		1.7
ClinPred		0.23	T
GERP RS		1.3
Varity_R		0.045
gMVP		0.38

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: rs935154773; hg19: chr7-138720475;