NM_213599.3:c.2236-12_2236-10dupTTT

Variant names:

• chr11-22274548-C-CTTT
• rs72105710
• NM_213599.3:c.2236-12_2236-10dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213599.3(ANO5):​c.2236-12_2236-10dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,119,940 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2236-12_2236-10dupTTT		intron	N/A	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.2233-12_2233-10dupTTT		intron	N/A	NP_001136121.1
	ANO5	NM_001410963.1		c.2194-12_2194-10dupTTT		intron	N/A	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.2236-21_2236-20insTTT		intron	N/A	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.2194-21_2194-20insTTT		intron	N/A	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.2191-21_2191-20insTTT		intron	N/A	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000179 AC: 2 AN: 1119940 Hom.: 0 Cov.: 0 AF XY: 0.00000181 AC XY: 1 AN XY: 553360

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25834

American (AMR) AF: 0.00 AC: 0 AN: 27504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18298

East Asian (EAS) AF: 0.00 AC: 0 AN: 28574

South Asian (SAS) AF: 0.0000161 AC: 1 AN: 61924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4644

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 866470

Other (OTH) AF: 0.00 AC: 0 AN: 46244

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69

Splicing

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

Other links and lift over

dbSNP: rs72105710; hg19: chr11-22296094;