11-22193331-AAGG-AAGGAGGAGGGGAATGAGGAGGAAGAGG

Variant names:

• chr11-22193331-A-AAGGAGGAGGGGAATGAGGAGGAAG
• rs71034576
• NM_213599.3:c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_213599.3(ANO5):​c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00022 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANO5 NM_213599.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 2 publications found

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]

ANO5 Gene-Disease associations (from GenCC):

• gnathodiaphyseal dysplasia

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2L

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Miyoshi muscular dystrophy 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00243 (367/150742) while in subpopulation AFR AF = 0.00874 (359/41078). AF 95% confidence interval is 0.00799. There are 1 homozygotes in GnomAd4. There are 162 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	NM_213599.3	MANE Select	c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG		5_prime_UTR	Exon 1 of 22	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG		5_prime_UTR	Exon 1 of 22	NP_001136121.1
	ANO5	NM_001410963.1		c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG		5_prime_UTR	Exon 1 of 21	NP_001397892.1	A0A804HL91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	ENST00000324559.9	TSL:1 MANE Select	c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG		5_prime_UTR	Exon 1 of 22	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG		5_prime_UTR	Exon 1 of 21	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.-156_-155insAGGGGAATGAGGAGGAAGAGGAGG		5_prime_UTR	Exon 1 of 21	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 366 AN: 150624 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00145

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000223 AC: 286 AN: 1279960 Hom.: 3 Cov.: 57 AF XY: 0.000208 AC XY: 129 AN XY: 620608

African (AFR) AF: 0.00917 AC: 258 AN: 28124

American (AMR) AF: 0.000281 AC: 8 AN: 28470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19334

East Asian (EAS) AF: 0.00 AC: 0 AN: 34020

South Asian (SAS) AF: 0.0000313 AC: 2 AN: 63796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4974

European-Non Finnish (NFE) AF: 0.00000295 AC: 3 AN: 1018606

Other (OTH) AF: 0.000284 AC: 15 AN: 52798

GnomAD4 genome AF: 0.00243 AC: 367 AN: 150742 Hom.: 1 Cov.: 0 AF XY: 0.00220 AC XY: 162 AN XY: 73576

African (AFR) AF: 0.00874 AC: 359 AN: 41078

American (AMR) AF: 0.000197 AC: 3 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10394

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67578

Other (OTH) AF: 0.00144 AC: 3 AN: 2084

Alfa AF: 0.00 Hom.: 1563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs71034576; hg19: chr11-22214877;