11-22193331-AAGG-AAGGAGGAGGGGAATGAGGAGGAGGAGG

Variant names:

• chr11-22193331-A-AAGGAGGAGGGGAATGAGGAGGAGG
• rs71034576
• NM_213599.3:c.-156_-155insAGGGGAATGAGGAGGAGGAGGAGG

Variant summary

Our verdict is Benign. The variant received -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. 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. 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
• 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 -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 VariationId 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.

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

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

African (AFR) AF: 0.899 AC: 25187 AN: 28020

American (AMR) AF: 0.591 AC: 16576 AN: 28066

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 13904 AN: 19144

East Asian (EAS) AF: 0.503 AC: 17027 AN: 33858

South Asian (SAS) AF: 0.778 AC: 49294 AN: 63368

European-Finnish (FIN) AF: 0.781 AC: 23199 AN: 29692

Middle Eastern (MID) AF: 0.803 AC: 3974 AN: 4946

European-Non Finnish (NFE) AF: 0.801 AC: 809911 AN: 1011090

Other (OTH) AF: 0.780 AC: 40865 AN: 52400

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

African (AFR) AF: 0.909 AC: 37323 AN: 41050

American (AMR) AF: 0.716 AC: 10871 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2602 AN: 3460

East Asian (EAS) AF: 0.551 AC: 2755 AN: 5002

South Asian (SAS) AF: 0.804 AC: 3811 AN: 4738

European-Finnish (FIN) AF: 0.816 AC: 8468 AN: 10376

Middle Eastern (MID) AF: 0.798 AC: 233 AN: 292

European-Non Finnish (NFE) AF: 0.811 AC: 54786 AN: 67526

Other (OTH) AF: 0.808 AC: 1681 AN: 2080

Alfa AF: 0.603 Hom.: 1563

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Gnathodiaphyseal dysplasia (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Miyoshi myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.2
Mutation Taster		=300/0	polymorphism (auto)

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;