2-241191216-C-T

Variant names:

• chr2-241191216-C-T
• NM_001370694.2:c.131C>T

Variant summary

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

The NM_001370694.2(ANO7):​c.131C>T​(p.Ala44Val) 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. 16/21 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)
• Consequence: ANO7 NM_001370694.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.51

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=0.059274286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO7	NM_001370694.2	c.131C>T	p.Ala44Val	missense_variant	Exon 3 of 25	ENST00000674324.2	NP_001357623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO7	ENST00000674324.2	c.131C>T	p.Ala44Val	missense_variant	Exon 3 of 25		NM_001370694.2	ENSP00000501393.1
ANO7	ENST00000274979.12	c.293C>T	p.Ala98Val	missense_variant	Exon 3 of 25	1		ENSP00000274979.8
ANO7	ENST00000402530.8	c.131C>T	p.Ala44Val	missense_variant	Exon 3 of 4	1		ENSP00000383985.4
ANO7	ENST00000402430.8	c.131C>T	p.Ala44Val	missense_variant	Exon 3 of 22	5		ENSP00000385418.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.293C>T (p.A98V) alteration is located in exon 3 (coding exon 3) of the ANO7 gene. This alteration results from a C to T substitution at nucleotide position 293, causing the alanine (A) at amino acid position 98 to be replaced by a valine (V). 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	0.085
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.64
DANN	Benign	0.94
DEOGEN2	Benign	0.034	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.056
Sift	Benign	0.073	T;T;T
Sift4G	Uncertain	0.028	D;T;T
Polyphen		0.48	P;B;.
Vest4		0.16
MutPred		0.28		Loss of disorder (P = 0.078);Loss of disorder (P = 0.078);Loss of disorder (P = 0.078);
MVP		0.099
MPC		0.12
ClinPred		0.053	T
GERP RS		1.1
Varity_R		0.023
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-242130631;