chr11-22193357-G-C

Variant names:

• chr11-22193357-G-C
• rs12792259
• NM_213599.3:c.-136G>C

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.-136G>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 0.826 in 151,762 control chromosomes in the GnomAD database, including 52,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52288 hom., cov: 29)
  • Exomes 𝑓: 0.80 (439941 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANO5 NM_213599.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9 O:1
• Conservation: PhyloP100: -1.24
• Publications: 17 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), 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, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.96).
• BP6: Variant 11-22193357-G-C is Benign according to our data. Variant chr11-22193357-G-C is described in ClinVar as Benign. ClinVar VariationId is 140544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 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.-136G>C		5_prime_UTR	Exon 1 of 22	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.-136G>C		5_prime_UTR	Exon 1 of 22	NP_001136121.1
	ANO5	NM_001410963.1		c.-136G>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.-136G>C		5_prime_UTR	Exon 1 of 22	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.-136G>C		5_prime_UTR	Exon 1 of 21	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.-136G>C		5_prime_UTR	Exon 1 of 21	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125232 AN: 151640 Hom.: 52231 Cov.: 29

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.813

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.799 AC: 1094554 AN: 1370602 Hom.: 439941 Cov.: 63 AF XY: 0.799 AC XY: 538657 AN XY: 674350

African (AFR) AF: 0.936 AC: 29320 AN: 31330

American (AMR) AF: 0.627 AC: 22009 AN: 35088

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 18349 AN: 24292

East Asian (EAS) AF: 0.518 AC: 18301 AN: 35328

South Asian (SAS) AF: 0.804 AC: 61900 AN: 76962

European-Finnish (FIN) AF: 0.809 AC: 28964 AN: 35800

Middle Eastern (MID) AF: 0.819 AC: 4591 AN: 5608

European-Non Finnish (NFE) AF: 0.810 AC: 865667 AN: 1069000

Other (OTH) AF: 0.795 AC: 45453 AN: 57194

GnomAD4 genome AF: 0.826 AC: 125352 AN: 151762 Hom.: 52288 Cov.: 29 AF XY: 0.823 AC XY: 61018 AN XY: 74140

African (AFR) AF: 0.930 AC: 38489 AN: 41390

American (AMR) AF: 0.719 AC: 10981 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2611 AN: 3468

East Asian (EAS) AF: 0.556 AC: 2830 AN: 5092

South Asian (SAS) AF: 0.806 AC: 3854 AN: 4784

European-Finnish (FIN) AF: 0.819 AC: 8636 AN: 10544

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55198 AN: 67904

Other (OTH) AF: 0.814 AC: 1716 AN: 2108

Alfa AF: 0.824 Hom.: 6063

Bravo AF: 0.815

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)
-	-	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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.48
PhyloP100		-1.2
PromoterAI		-0.21	Neutral
Mutation Taster		=298/2	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: rs12792259; hg19: chr11-22214903; COSMIC: COSV61083375;