2-241191209-G-A

Variant summary

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

The NM_001370694.2(ANO7):c.124G>A(p.Ala42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 (0 hom.)
• Consequence: ANO7 NM_001370694.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.531

Genes affected

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

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=0.050513297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO7	NM_001370694.2	c.124G>A	p.Ala42Thr	missense_variant	3/25	ENST00000674324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO7	ENST00000674324.2	c.124G>A	p.Ala42Thr	missense_variant	3/25		NM_001370694.2	A2
ANO7	ENST00000274979.12	c.286G>A	p.Ala96Thr	missense_variant	3/25	1		P2
ANO7	ENST00000402530.8	c.124G>A	p.Ala42Thr	missense_variant	3/4	1
ANO7	ENST00000402430.8	c.124G>A	p.Ala42Thr	missense_variant	3/22	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251156 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461564 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.286G>A (p.A96T) alteration is located in exon 3 (coding exon 3) of the ANO7 gene. This alteration results from a G to A substitution at nucleotide position 286, causing the alanine (A) at amino acid position 96 to be replaced by a threonine (T). 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	0.080
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	5.5
Dann	Uncertain	0.98
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.051	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.57	N;N;N
REVEL	Benign	0.035
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.068	T;T;T
Polyphen		0.21	B;B;.
Vest4		0.13
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.16
MPC		0.11
ClinPred		0.022	T
GERP RS		2.0
Varity_R		0.048
gMVP		0.088

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: rs199899635; hg19: chr2-242130624;