rs77453551

Variant names:

• chr3-43690694-A-T
• rs77453551
• ENST00000910681.1:c.-363T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001346468.2(ANO10):​c.-12+823T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 379,850 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (4 hom.)
• Consequence: ANO10 NM_001346468.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00
• Publications: 1 publications found

Genes affected

ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ABHD5 (HGNC:21396): (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [provided by RefSeq, Jul 2008]

ABHD5 Gene-Disease associations (from GenCC):

• Dorfman-Chanarin disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-43690694-A-T is Benign according to our data. Variant chr3-43690694-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1333046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00864 (1316/152276) while in subpopulation AFR AF = 0.0286 (1191/41574). AF 95% confidence interval is 0.0273. There are 22 homozygotes in GnomAd4. There are 623 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346468.2. 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
	ANO10	NM_001346468.2		c.-12+823T>A		intron	N/A	NP_001333397.1	Q9NW15-1
	ANO10	NM_001346469.2		c.-12+823T>A		intron	N/A	NP_001333398.1	Q9NW15-3
	ABHD5	NM_016006.6	MANE Select	c.-299A>T		upstream_gene	N/A	NP_057090.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000910681.1		c.-363T>A		5_prime_UTR	Exon 1 of 15	ENSP00000580740.1
	ABHD5	ENST00000456453.5	TSL:4	c.-93A>T		5_prime_UTR	Exon 2 of 4	ENSP00000391582.1	C9JBM3
	ANO10	ENST00000428831.1	TSL:5	c.-185T>A		5_prime_UTR	Exon 1 of 4	ENSP00000406712.1	C9IZD0

Frequencies

GnomAD3 genomes AF: 0.00864 AC: 1315 AN: 152158 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00768

GnomAD4 exome AF: 0.00129 AC: 294 AN: 227574 Hom.: 4 Cov.: 0 AF XY: 0.00135 AC XY: 157 AN XY: 116070

African (AFR) AF: 0.0274 AC: 167 AN: 6100

American (AMR) AF: 0.00473 AC: 30 AN: 6336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8014

East Asian (EAS) AF: 0.00 AC: 0 AN: 19956

South Asian (SAS) AF: 0.000206 AC: 1 AN: 4864

European-Finnish (FIN) AF: 0.0000492 AC: 1 AN: 20312

Middle Eastern (MID) AF: 0.000859 AC: 1 AN: 1164

European-Non Finnish (NFE) AF: 0.000274 AC: 40 AN: 146040

Other (OTH) AF: 0.00365 AC: 54 AN: 14788

GnomAD4 genome AF: 0.00864 AC: 1316 AN: 152276 Hom.: 22 Cov.: 32 AF XY: 0.00837 AC XY: 623 AN XY: 74476

African (AFR) AF: 0.0286 AC: 1191 AN: 41574

American (AMR) AF: 0.00568 AC: 87 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67998

Other (OTH) AF: 0.00760 AC: 16 AN: 2104

Alfa AF: 0.00707 Hom.: 1

Bravo AF: 0.0102

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.40
PhyloP100		0.0
PromoterAI		0.028	Neutral

Splicing

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

Other links and lift over

dbSNP: rs77453551; hg19: chr3-43732186;