rs79436573

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-43690745-C-G
• chr3-43690745-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001346468.2(ANO10):​c.-12+772G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 274,492 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: ANO10 NM_001346468.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• 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: 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=-0.81).

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+772G>C		intron	N/A	NP_001333397.1	Q9NW15-1
	ANO10	NM_001346469.2		c.-12+772G>C		intron	N/A	NP_001333398.1	Q9NW15-3
	ABHD5	NM_016006.6	MANE Select	c.-248C>G		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>C		5_prime_UTR	Exon 1 of 14	ENSP00000640624.1
	ANO10	ENST00000428831.1	TSL:5	c.-236G>C		5_prime_UTR	Exon 1 of 4	ENSP00000406712.1	C9IZD0
	ANO10	ENST00000436073.1	TSL:4	c.-307G>C		5_prime_UTR	Exon 1 of 3	ENSP00000404988.1	C9JJS5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000364 AC: 1 AN: 274492 Hom.: 0 Cov.: 2 AF XY: 0.00000705 AC XY: 1 AN XY: 141756

African (AFR) AF: 0.00 AC: 0 AN: 6636

American (AMR) AF: 0.00 AC: 0 AN: 6922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9296

East Asian (EAS) AF: 0.00 AC: 0 AN: 21396

South Asian (SAS) AF: 0.00 AC: 0 AN: 11988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1328

European-Non Finnish (NFE) AF: 0.00000569 AC: 1 AN: 175690

Other (OTH) AF: 0.00 AC: 0 AN: 17368

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.082
DANN	Benign	0.43
PhyloP100		-2.6
PromoterAI		0.18	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;