rs181864243

Variant names:

• chr11-22193283-G-C
• rs181864243
• NM_213599.3:c.-210G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_213599.3(ANO5):​c.-210G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,110,696 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (6 hom.)
• Consequence: ANO5 NM_213599.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: -3.71
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS2: High Homozygotes in GnomAdExome4 at 6 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.-210G>C		5_prime_UTR	Exon 1 of 22	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.-210G>C		5_prime_UTR	Exon 1 of 22	NP_001136121.1
	ANO5	NM_001410963.1		c.-210G>C		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.-210G>C		5_prime_UTR	Exon 1 of 22	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.-210G>C		5_prime_UTR	Exon 1 of 21	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.-210G>C		5_prime_UTR	Exon 1 of 21	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 192 AN: 115802 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000339

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00143

Gnomad FIN AF: 0.00589

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.00189

GnomAD4 exome AF: 0.00250 AC: 2487 AN: 994838 Hom.: 6 Cov.: 29 AF XY: 0.00248 AC XY: 1165 AN XY: 469516

African (AFR) AF: 0.000715 AC: 16 AN: 22368

American (AMR) AF: 0.00 AC: 0 AN: 12070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10214

East Asian (EAS) AF: 0.00 AC: 0 AN: 20104

South Asian (SAS) AF: 0.00122 AC: 39 AN: 31922

European-Finnish (FIN) AF: 0.0137 AC: 131 AN: 9582

Middle Eastern (MID) AF: 0.00165 AC: 4 AN: 2428

European-Non Finnish (NFE) AF: 0.00260 AC: 2208 AN: 849472

Other (OTH) AF: 0.00243 AC: 89 AN: 36678

GnomAD4 genome AF: 0.00166 AC: 192 AN: 115858 Hom.: 1 Cov.: 31 AF XY: 0.00177 AC XY: 99 AN XY: 56052

African (AFR) AF: 0.000344 AC: 10 AN: 29046

American (AMR) AF: 0.000338 AC: 4 AN: 11824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2906

East Asian (EAS) AF: 0.00 AC: 0 AN: 4274

South Asian (SAS) AF: 0.00143 AC: 5 AN: 3490

European-Finnish (FIN) AF: 0.00589 AC: 44 AN: 7464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.00232 AC: 126 AN: 54350

Other (OTH) AF: 0.00186 AC: 3 AN: 1610

Alfa AF: 0.00140 Hom.: 0

Bravo AF: 0.000971

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	ANO5-Related Muscle Diseases (1)
-	1	-	Limb-girdle muscular dystrophy, recessive (1)
-	1	-	Miyoshi myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.40
PhyloP100		-3.7
PromoterAI		-0.026	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs181864243; hg19: chr11-22214829;