NM_016006.6:c.-19C>T

Variant names:

• chr3-43690974-C-T
• rs117630969
• NM_016006.6:c.-19C>T

Variant summary

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

The NM_016006.6(ABHD5):​c.-19C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,568,598 control chromosomes in the GnomAD database, including 894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (56 hom., cov: 32)
  • Exomes 𝑓: 0.028 (838 hom.)
• Consequence: ABHD5 NM_016006.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.30
• Publications: 4 publications found

Genes affected

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]

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]

ANO10 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 10

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-43690974-C-T is Benign according to our data. Variant chr3-43690974-C-T is described in ClinVar as Benign. ClinVar VariationId is 345213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016006.6. 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
	ABHD5	NM_016006.6	MANE Select	c.-19C>T		5_prime_UTR	Exon 1 of 7	NP_057090.2
	ABHD5	NM_001355186.2		c.-19C>T		5_prime_UTR	Exon 1 of 8	NP_001342115.1	Q8WTS1
	ABHD5	NM_001365650.1		c.-19C>T		5_prime_UTR	Exon 1 of 6	NP_001352579.1	A0A2U3TZT9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD5	ENST00000644371.2	MANE Select	c.-19C>T		5_prime_UTR	Exon 1 of 7	ENSP00000495778.1	Q8WTS1
	ABHD5	ENST00000458276.7	TSL:1	c.-19C>T		5_prime_UTR	Exon 1 of 6	ENSP00000390849.3	A0A2U3TZT9
	ABHD5	ENST00000967519.1		c.-19C>T		5_prime_UTR	Exon 1 of 8	ENSP00000637578.1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3209 AN: 152000 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.00785

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.00500

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0249

GnomAD2 exomes AF: 0.0320 AC: 6336 AN: 197706 AF XY: 0.0363

Gnomad AFR exome AF: 0.00818

Gnomad AMR exome AF: 0.0285

Gnomad ASJ exome AF: 0.0300

Gnomad EAS exome AF: 0.0216

Gnomad FIN exome AF: 0.00739

Gnomad NFE exome AF: 0.0241

Gnomad OTH exome AF: 0.0267

GnomAD4 exome AF: 0.0281 AC: 39762 AN: 1416490 Hom.: 838 Cov.: 31 AF XY: 0.0302 AC XY: 21256 AN XY: 704468

African (AFR) AF: 0.00667 AC: 196 AN: 29388

American (AMR) AF: 0.0301 AC: 1209 AN: 40148

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 774 AN: 24802

East Asian (EAS) AF: 0.0300 AC: 1036 AN: 34586

South Asian (SAS) AF: 0.0904 AC: 7381 AN: 81648

European-Finnish (FIN) AF: 0.00746 AC: 364 AN: 48772

Middle Eastern (MID) AF: 0.0450 AC: 251 AN: 5576

European-Non Finnish (NFE) AF: 0.0245 AC: 26754 AN: 1093116

Other (OTH) AF: 0.0307 AC: 1797 AN: 58454

GnomAD4 genome AF: 0.0211 AC: 3214 AN: 152108 Hom.: 56 Cov.: 32 AF XY: 0.0214 AC XY: 1593 AN XY: 74366

African (AFR) AF: 0.00799 AC: 332 AN: 41536

American (AMR) AF: 0.0233 AC: 356 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.0265 AC: 136 AN: 5140

South Asian (SAS) AF: 0.0917 AC: 442 AN: 4820

European-Finnish (FIN) AF: 0.00500 AC: 53 AN: 10590

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0256 AC: 1740 AN: 67954

Other (OTH) AF: 0.0247 AC: 52 AN: 2108

Alfa AF: 0.0222 Hom.: 18

Bravo AF: 0.0202

Asia WGS AF: 0.0460 AC: 158 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Triglyceride storage disease with ichthyosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.28
DANN	Benign	0.94
PhyloP100		-2.3
PromoterAI		-0.26	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117630969; hg19: chr3-43732466; COSMIC: COSV50006580; COSMIC: COSV50006580;