ENST00000970565.1:c.-220G>A

Variant names:

• chr3-43690745-C-T
• rs79436573
• ENST00000970565.1:c.-220G>A

Variant summary

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

The ENST00000970565.1(ANO10):​c.-220G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 426,546 control chromosomes in the GnomAD database, including 174 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 (119 hom.)
• Consequence: ANO10 ENST00000970565.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.57
• 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=-0.8).
• BP6: Variant 3-43690745-C-T is Benign according to our data. Variant chr3-43690745-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 670436.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: ENST00000970565.1. 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+772G>A		intron	N/A	NP_001333397.1	Q9NW15-1
	ANO10	NM_001346469.2		c.-12+772G>A		intron	N/A	NP_001333398.1	Q9NW15-3
	ABHD5	NM_016006.6	MANE Select	c.-248C>T		upstream_gene	N/A	NP_057090.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000970565.1		c.-220G>A		5_prime_UTR	Exon 1 of 14	ENSP00000640624.1
	ANO10	ENST00000428831.1	TSL:5	c.-236G>A		5_prime_UTR	Exon 1 of 4	ENSP00000406712.1	C9IZD0
	ANO10	ENST00000436073.1	TSL:4	c.-307G>A		5_prime_UTR	Exon 1 of 3	ENSP00000404988.1	C9JJS5

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3207 AN: 152198 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.00781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0253 AC: 6932 AN: 274230 Hom.: 119 Cov.: 2 AF XY: 0.0266 AC XY: 3770 AN XY: 141602

African (AFR) AF: 0.00724 AC: 48 AN: 6634

American (AMR) AF: 0.0384 AC: 265 AN: 6910

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 301 AN: 9292

East Asian (EAS) AF: 0.0326 AC: 698 AN: 21382

South Asian (SAS) AF: 0.0658 AC: 784 AN: 11912

European-Finnish (FIN) AF: 0.00729 AC: 174 AN: 23854

Middle Eastern (MID) AF: 0.0520 AC: 69 AN: 1328

European-Non Finnish (NFE) AF: 0.0237 AC: 4167 AN: 175558

Other (OTH) AF: 0.0245 AC: 426 AN: 17360

GnomAD4 genome AF: 0.0211 AC: 3212 AN: 152316 Hom.: 55 Cov.: 33 AF XY: 0.0214 AC XY: 1594 AN XY: 74472

African (AFR) AF: 0.00796 AC: 331 AN: 41594

American (AMR) AF: 0.0232 AC: 355 AN: 15304

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

East Asian (EAS) AF: 0.0270 AC: 139 AN: 5152

South Asian (SAS) AF: 0.0917 AC: 443 AN: 4830

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: 1736 AN: 68020

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

Alfa AF: 0.0209 Hom.: 7

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	-0.80
CADD	Benign	0.12
DANN	Benign	0.88
PhyloP100		-2.6
PromoterAI		0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs79436573; hg19: chr3-43732237;