rs140903276

Variant names:

• chr11-22236194-G-A
• NM_213599.3:c.680G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-22236194-G-A
• chr11-22236194-G-C

Variant summary

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

The NM_213599.3(ANO5):​c.680G>A​(p.Gly227Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,904 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G227A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANO5 NM_213599.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

Genes affected

ANO5 (HGNC:27337): (anoctamin 5) This gene encodes a member of the anoctamin family of transmembrane proteins. The encoded protein is likely a calcium activated chloride channel. Mutations in this gene have been associated with gnathodiaphyseal dysplasia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3	c.680G>A	p.Gly227Asp	missense_variant	Exon 8 of 22	ENST00000324559.9	NP_998764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9	c.680G>A	p.Gly227Asp	missense_variant	Exon 8 of 22	1	NM_213599.3	ENSP00000315371.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460904 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726804

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.25
Sift	Benign	0.54	T
Sift4G	Benign	0.58	T
Polyphen		0.97	D
Vest4		0.52
MutPred		0.48		Loss of catalytic residue at G227 (P = 0.0523);
MVP		0.65
MPC		0.46
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.15
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-22257740; COSMIC: COSV61087105;