rs4312063

Variant names:

• chr11-22221183-T-C
• rs4312063
• NM_213599.3:c.267T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-22221183-T-C
• chr11-22221183-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_213599.3(ANO5):​c.267T>C​(p.Asp89Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,610,396 control chromosomes in the GnomAD database, including 518,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52348 hom., cov: 32)
  • Exomes 𝑓: 0.80 (466471 hom.)
• Consequence: ANO5 NM_213599.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:19 O:2
• Conservation: PhyloP100: -0.700
• Publications: 27 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-22221183-T-C is Benign according to our data. Variant chr11-22221183-T-C is described in ClinVar as Benign. ClinVar VariationId is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.7 with no splicing effect.
• 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.267T>C	p.Asp89Asp	synonymous	Exon 5 of 22	NP_998764.1	Q75V66
	ANO5	NM_001142649.2		c.264T>C	p.Asp88Asp	synonymous	Exon 5 of 22	NP_001136121.1
	ANO5	NM_001410963.1		c.225T>C	p.Asp75Asp	synonymous	Exon 4 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.267T>C	p.Asp89Asp	synonymous	Exon 5 of 22	ENSP00000315371.9	Q75V66
	ANO5	ENST00000682341.1		c.225T>C	p.Asp75Asp	synonymous	Exon 4 of 21	ENSP00000508251.1	A0A804HL91
	ANO5	ENST00000684663.1		c.222T>C	p.Asp74Asp	synonymous	Exon 4 of 21	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125391 AN: 151818 Hom.: 52294 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.810

GnomAD2 exomes AF: 0.766 AC: 191380 AN: 249920 AF XY: 0.772

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.601

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.820

Gnomad NFE exome AF: 0.807

Gnomad OTH exome AF: 0.780

GnomAD4 exome AF: 0.797 AC: 1162290 AN: 1458460 Hom.: 466471 Cov.: 42 AF XY: 0.797 AC XY: 578577 AN XY: 725672

African (AFR) AF: 0.936 AC: 31206 AN: 33352

American (AMR) AF: 0.615 AC: 27396 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 19600 AN: 26052

East Asian (EAS) AF: 0.527 AC: 20827 AN: 39518

South Asian (SAS) AF: 0.803 AC: 69175 AN: 86154

European-Finnish (FIN) AF: 0.812 AC: 43266 AN: 53288

Middle Eastern (MID) AF: 0.818 AC: 4696 AN: 5744

European-Non Finnish (NFE) AF: 0.810 AC: 898327 AN: 1109632

Other (OTH) AF: 0.794 AC: 47797 AN: 60198

GnomAD4 genome AF: 0.826 AC: 125507 AN: 151936 Hom.: 52348 Cov.: 32 AF XY: 0.823 AC XY: 61097 AN XY: 74240

African (AFR) AF: 0.930 AC: 38624 AN: 41520

American (AMR) AF: 0.719 AC: 10951 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2612 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2877 AN: 5146

South Asian (SAS) AF: 0.806 AC: 3885 AN: 4820

European-Finnish (FIN) AF: 0.820 AC: 8672 AN: 10580

Middle Eastern (MID) AF: 0.805 AC: 235 AN: 292

European-Non Finnish (NFE) AF: 0.813 AC: 55138 AN: 67852

Other (OTH) AF: 0.812 AC: 1713 AN: 2110

Alfa AF: 0.806 Hom.: 68620

Bravo AF: 0.815

Asia WGS AF: 0.724 AC: 2518 AN: 3474

EpiCase AF: 0.800

EpiControl AF: 0.800

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	10	not specified (10)
-	-	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	Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Miyoshi muscular dystrophy 3 (1)
-	-	1	Miyoshi myopathy (1)
-	-	-	ANO5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.36
PhyloP100		-0.70
Mutation Taster		=100/0	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: rs4312063; hg19: chr11-22242729; COSMIC: COSV61084691;