2-241191246-G-C

Variant names:

• chr2-241191246-G-C
• rs141913177
• NM_001370694.2:c.161G>C

Variant summary

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

The NM_001370694.2(ANO7):​c.161G>C​(p.Arg54Pro) 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 1,461,446 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANO7 NM_001370694.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 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=0.07204792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO7	NM_001370694.2	c.161G>C	p.Arg54Pro	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.161G>C	p.Arg54Pro	missense_variant	Exon 3 of 25		NM_001370694.2	ENSP00000501393.1
ANO7	ENST00000274979.12	c.323G>C	p.Arg108Pro	missense_variant	Exon 3 of 25	1		ENSP00000274979.8
ANO7	ENST00000402530.8	c.161G>C	p.Arg54Pro	missense_variant	Exon 3 of 4	1		ENSP00000383985.4
ANO7	ENST00000402430.8	c.161G>C	p.Arg54Pro	missense_variant	Exon 3 of 22	5		ENSP00000385418.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461446 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727068

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.071	.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.32	T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.55	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.21	T;D;T
Sift4G	Pathogenic	0.0	D;D;T
Polyphen		0.0040	B;B;.
Vest4		0.41
MutPred		0.47		Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);
MVP		0.30
MPC		0.16
ClinPred		0.10	T
GERP RS		-1.2
Varity_R		0.20
gMVP		0.57

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: rs141913177; hg19: chr2-242130661;