11-22193276-G-T

Variant names:

• chr11-22193276-G-T
• rs73479393
• NM_213599.3:c.-217G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_213599.3(ANO5):​c.-217G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,175,138 control chromosomes in the GnomAD database, including 1,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (878 hom., cov: 31)
  • Exomes 𝑓: 0.0071 (673 hom.)
• Consequence: ANO5 NM_213599.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.70
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-22193276-G-T is Benign according to our data. Variant chr11-22193276-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 304090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 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.-217G>T		5_prime_UTR	Exon 1 of 22	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.-217G>T		5_prime_UTR	Exon 1 of 22	NP_001136121.1
	ANO5	NM_001410963.1		c.-217G>T		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.-217G>T		5_prime_UTR	Exon 1 of 22	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.-217G>T		5_prime_UTR	Exon 1 of 21	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.-217G>T		5_prime_UTR	Exon 1 of 21	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 8848 AN: 141944 Hom.: 881 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000693

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0433

GnomAD4 exome AF: 0.00708 AC: 7315 AN: 1033102 Hom.: 673 Cov.: 29 AF XY: 0.00645 AC XY: 3159 AN XY: 489642

African (AFR) AF: 0.253 AC: 5857 AN: 23154

American (AMR) AF: 0.0184 AC: 246 AN: 13374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11476

East Asian (EAS) AF: 0.0000442 AC: 1 AN: 22614

South Asian (SAS) AF: 0.000653 AC: 23 AN: 35248

European-Finnish (FIN) AF: 0.0000835 AC: 1 AN: 11974

Middle Eastern (MID) AF: 0.0105 AC: 27 AN: 2570

European-Non Finnish (NFE) AF: 0.000560 AC: 489 AN: 873658

Other (OTH) AF: 0.0172 AC: 671 AN: 39034

GnomAD4 genome AF: 0.0623 AC: 8846 AN: 142036 Hom.: 878 Cov.: 31 AF XY: 0.0602 AC XY: 4155 AN XY: 69046

African (AFR) AF: 0.218 AC: 8460 AN: 38762

American (AMR) AF: 0.0178 AC: 252 AN: 14186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3330

East Asian (EAS) AF: 0.00 AC: 0 AN: 4784

South Asian (SAS) AF: 0.000232 AC: 1 AN: 4316

European-Finnish (FIN) AF: 0.000103 AC: 1 AN: 9690

Middle Eastern (MID) AF: 0.00403 AC: 1 AN: 248

European-Non Finnish (NFE) AF: 0.000720 AC: 46 AN: 63888

Other (OTH) AF: 0.0429 AC: 85 AN: 1982

Alfa AF: 0.0182 Hom.: 94

Bravo AF: 0.0663

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ANO5-Related Muscle Diseases (1)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2L (1)
-	-	1	Gnathodiaphyseal dysplasia (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Miyoshi muscular dystrophy 3 (1)
-	-	1	Miyoshi myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		1.7
PromoterAI		-0.024	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs73479393; hg19: chr11-22214822;