7-139035783-C-T

Variant names:

• chr7-139035783-C-T
• rs1375382518
• NM_080660.4:c.235G>A

Variant summary

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

The NM_080660.4(ZC3HAV1L):​c.235G>A​(p.Ala79Thr) 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. 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. A79S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZC3HAV1L NM_080660.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 1 publications found

Genes affected

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

ENSG00000304140 (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=0.14900538).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080660.4. 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
	ZC3HAV1L	NM_080660.4	MANE Select	c.235G>A	p.Ala79Thr	missense	Exon 1 of 5	NP_542391.2	Q96H79-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3HAV1L	ENST00000275766.2	TSL:1 MANE Select	c.235G>A	p.Ala79Thr	missense	Exon 1 of 5	ENSP00000275766.1	Q96H79-1
	ENSG00000304140	ENST00000799991.1		n.303+443C>T		intron	N/A
	ENSG00000304140	ENST00000799992.1		n.-1C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 88936 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1341158 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 660974

African (AFR) AF: 0.00 AC: 0 AN: 27004

American (AMR) AF: 0.00 AC: 0 AN: 30030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23514

East Asian (EAS) AF: 0.00 AC: 0 AN: 30722

South Asian (SAS) AF: 0.00 AC: 0 AN: 74534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062020

Other (OTH) AF: 0.00 AC: 0 AN: 55938

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.00045	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.51	N
PhyloP100		-0.62
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.076
Sift	Benign	0.23	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.037
MutPred		0.34		Gain of sheet (P = 0.0101)
MVP		0.16
MPC		2.1
ClinPred		0.67	D
GERP RS		2.9
PromoterAI		-0.23	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.040
gMVP		0.071
Mutation Taster		=91/9	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: rs1375382518; hg19: chr7-138720529; COSMIC: COSV108774243;