11-22193331-AAGG-AAGGAGGAGGGTAATGAGGAGGAGGAGG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 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 0.0029 (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
• 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

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_-155insAGGGTAATGAGGAGGAGGAGGAGG		5_prime_UTR	Exon 1 of 22	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG		5_prime_UTR	Exon 1 of 22	NP_001136121.1
	ANO5	NM_001410963.1		c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG		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_-155insAGGGTAATGAGGAGGAGGAGGAGG		5_prime_UTR	Exon 1 of 22	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG		5_prime_UTR	Exon 1 of 21	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.-156_-155insAGGGTAATGAGGAGGAGGAGGAGG		5_prime_UTR	Exon 1 of 21	ENSP00000508009.1	A0A804HKP2

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

African (AFR) AF: 0.0112 AC: 314 AN: 28124

American (AMR) AF: 0.000421 AC: 12 AN: 28472

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: 0.0000196 AC: 20 AN: 1018602

Other (OTH) AF: 0.000549 AC: 29 AN: 52800

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

African (AFR) AF: 0.0101 AC: 414 AN: 41078

American (AMR) AF: 0.000987 AC: 15 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: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67578

Other (OTH) AF: 0.000480 AC: 1 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
Mutation Taster		=300/0	polymorphism

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;