3-43690751-G-A

Variant names:

• chr3-43690751-G-A
• rs116844757
• ENST00000970565.1:c.-226C>T

Variant summary

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

The NM_001346468.2(ANO10):​c.-12+766C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 427,052 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (55 hom., cov: 33)
  • Exomes 𝑓: 0.025 (121 hom.)
• Consequence: ANO10 NM_001346468.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.316
• Publications: 0 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=-0.76).
• BP6: Variant 3-43690751-G-A is Benign according to our data. Variant chr3-43690751-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 670437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

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+766C>T		intron	N/A	NP_001333397.1	Q9NW15-1
	ANO10	NM_001346469.2		c.-12+766C>T		intron	N/A	NP_001333398.1	Q9NW15-3
	ABHD5	NM_016006.6	MANE Select	c.-242G>A		upstream_gene	N/A	NP_057090.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000970565.1		c.-226C>T		5_prime_UTR	Exon 1 of 14	ENSP00000640624.1
	ANO10	ENST00000428831.1	TSL:5	c.-242C>T		5_prime_UTR	Exon 1 of 4	ENSP00000406712.1	C9IZD0
	ANO10	ENST00000436073.1	TSL:4	c.-313C>T		5_prime_UTR	Exon 1 of 3	ENSP00000404988.1	C9JJS5

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3210 AN: 152172 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.00789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0274

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0253

GnomAD4 exome AF: 0.0254 AC: 6990 AN: 274760 Hom.: 121 Cov.: 3 AF XY: 0.0268 AC XY: 3807 AN XY: 141824

African (AFR) AF: 0.00736 AC: 49 AN: 6660

American (AMR) AF: 0.0382 AC: 265 AN: 6938

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 300 AN: 9296

East Asian (EAS) AF: 0.0326 AC: 699 AN: 21420

South Asian (SAS) AF: 0.0674 AC: 806 AN: 11950

European-Finnish (FIN) AF: 0.00726 AC: 173 AN: 23820

Middle Eastern (MID) AF: 0.0523 AC: 70 AN: 1338

European-Non Finnish (NFE) AF: 0.0239 AC: 4202 AN: 175944

Other (OTH) AF: 0.0245 AC: 426 AN: 17394

GnomAD4 genome AF: 0.0211 AC: 3215 AN: 152292 Hom.: 55 Cov.: 33 AF XY: 0.0214 AC XY: 1594 AN XY: 74460

African (AFR) AF: 0.00803 AC: 334 AN: 41582

American (AMR) AF: 0.0232 AC: 355 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3472

East Asian (EAS) AF: 0.0271 AC: 139 AN: 5136

South Asian (SAS) AF: 0.0918 AC: 443 AN: 4828

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10626

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1735 AN: 68018

Other (OTH) AF: 0.0250 AC: 53 AN: 2116

Alfa AF: 0.00840 Hom.: 4

Bravo AF: 0.0202

Asia WGS AF: 0.0450 AC: 157 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	-0.76
CADD	Benign	5.4
DANN	Benign	0.90
PhyloP100		0.32
PromoterAI		0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs116844757; hg19: chr3-43732243;