chr11-22193331-A-AAGGAGGAGGGGAATGAGGAGGAGG

Position:

• chr11-22193331-A-AAGGAGGAGGGGAATGAGGAGGAGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_213599.3(ANO5):​c.-156_-155insAGGGGAATGAGGAGGAGGAGGAGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50911 hom., cov: 0)
  • Exomes 𝑓: 0.79 (394924 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANO5 NM_213599.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.16

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 11-22193331-A-AAGGAGGAGGGGAATGAGGAGGAGG is Benign according to our data. Variant chr11-22193331-A-AAGGAGGAGGGGAATGAGGAGGAGG is described in ClinVar as [Benign]. Clinvar id is 304093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO5	NM_213599.3	c.-156_-155insAGGGGAATGAGGAGGAGGAGGAGG		5_prime_UTR_variant	1/22	ENST00000324559.9	NP_998764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9	c.-156_-155insAGGGGAATGAGGAGGAGGAGGAGG		5_prime_UTR_variant	1/22	1	NM_213599.3	ENSP00000315371	P2

Frequencies

GnomAD3 genomes AF: 0.819 AC: 123203 AN: 150488 Hom.: 50858 Cov.: 0

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.807

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.787 AC: 999937 AN: 1270584 Hom.: 394924 Cov.: 57 AF XY: 0.786 AC XY: 484315 AN XY: 616144

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.726

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.778

Gnomad4 FIN exome AF: 0.781

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.780

GnomAD4 genome AF: 0.819 AC: 123317 AN: 150606 Hom.: 50911 Cov.: 0 AF XY: 0.816 AC XY: 59991 AN XY: 73484

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.808

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Limb-girdle muscular dystrophy, recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Gnathodiaphyseal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Miyoshi myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71034576; hg19: chr11-22214877;