11-22193331-AAGG-AAGGAGGAGGGTAATGAGGAGGAGGAGG

Variant names:

• chr11-22193331-A-AAGGAGGAGGGTAATGAGGAGGAGG
• rs71034576
• NM_213599.3:c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_213599.3(ANO5):​c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 0)
  • Exomes 𝑓: 0.00029 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANO5 NM_213599.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00288 (434/150742) while in subpopulation AFR AF= 0.0101 (414/41078). AF 95% confidence interval is 0.00928. There are 3 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 434 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3	c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG		5_prime_UTR_variant	Exon 1 of 22	ENST00000324559.9	NP_998764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559	c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG		5_prime_UTR_variant	Exon 1 of 22	1	NM_213599.3	ENSP00000315371.9

Frequencies

GnomAD3 genomes AF: 0.00287 AC: 432 AN: 150624 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000592

Gnomad OTH AF: 0.000485

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000295 AC: 377 AN: 1279960 Hom.: 2 Cov.: 57 AF XY: 0.000263 AC XY: 163 AN XY: 620608

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.000421

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000313

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000196

Gnomad4 OTH exome AF: 0.000549

GnomAD4 genome AF: 0.00288 AC: 434 AN: 150742 Hom.: 3 Cov.: 0 AF XY: 0.00254 AC XY: 187 AN XY: 73574

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.000987

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000592

Gnomad4 OTH AF: 0.000480

ClinVar

Not reported in ClinVar

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;