dbSNP rs1268671175: ANO5:c.-251T>C (chr11-22193242-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_213599.3(ANO5):c.-251T>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 0.00000715 in 139,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANO5
NM_213599.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

Publications

0 publications found

Variant links:

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)

ANO5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO5	NM_213599.3	MANE Select	c.-251T>C	5_prime_UTR	Exon 1 of 22	NP_998764.1	Q75V66
ANO5	NM_001142649.2		c.-251T>C	5_prime_UTR	Exon 1 of 22	NP_001136121.1
ANO5	NM_001410963.1		c.-251T>C	5_prime_UTR	Exon 1 of 21	NP_001397892.1	A0A804HL91

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO5	ENST00000324559.9	TSL:1 MANE Select	c.-251T>C	5_prime_UTR	Exon 1 of 22	ENSP00000315371.9	Q75V66
ANO5	ENST00000682341.1		c.-251T>C	5_prime_UTR	Exon 1 of 21	ENSP00000508251.1	A0A804HL91
ANO5	ENST00000684663.1		c.-251T>C	5_prime_UTR	Exon 1 of 21	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes

AF:

0.00000715

AC:

AN:

139898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000102

AC:

AN:

982496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

463952

show subpopulations

African (AFR)

AF:

0.0000513

AC:

AN:

19488

American (AMR)

AF:

0.00

AC:

AN:

9452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9830

East Asian (EAS)

AF:

0.00

AC:

AN:

18720

South Asian (SAS)

AF:

0.00

AC:

AN:

31026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2362

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

847230

Other (OTH)

AF:

0.00

AC:

AN:

35728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000715

AC:

AN:

139898

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

68100

show subpopulations

African (AFR)

AF:

0.0000271

AC:

AN:

36950

American (AMR)

AF:

0.00

AC:

AN:

14106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3272

East Asian (EAS)

AF:

0.00

AC:

AN:

4814

South Asian (SAS)

AF:

0.00

AC:

AN:

4280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63848

Other (OTH)

AF:

0.00

AC:

AN:

1928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.42

PhyloP100

-2.4

PromoterAI

0.00060

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over