rs141400669

Variant names:

• chr3-43372837-C-T
• rs141400669
• NM_018075.5:c.1915-5863G>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_018075.5(ANO10):​c.1915-5863G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,535,384 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (4 hom.)
• Consequence: ANO10 NM_018075.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.31
• Publications: 2 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]

SNRK (HGNC:30598): (SNF related kinase) SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002 [PubMed 12234663]).[supplied by OMIM, Apr 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004222065).
• BP6: Variant 3-43372837-C-T is Benign according to our data. Variant chr3-43372837-C-T is described in ClinVar as Benign. ClinVar VariationId is 446832.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 = 0.0046 (701/152334) while in subpopulation AFR AF = 0.0162 (674/41576). AF 95% confidence interval is 0.0152. There are 3 homozygotes in GnomAd4. There are 313 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018075.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	NM_018075.5	MANE Select	c.1915-5863G>A		intron	N/A	NP_060545.3
	ANO10	NM_001204831.3		c.1808G>A	p.Cys603Tyr	missense	Exon 12 of 13	NP_001191760.1
	ANO10	NM_001346464.2		c.2032-5863G>A		intron	N/A	NP_001333393.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO10	ENST00000292246.8	TSL:1 MANE Select	c.1915-5863G>A		intron	N/A	ENSP00000292246.3
	ANO10	ENST00000350459.8	TSL:1	c.1345-5863G>A		intron	N/A	ENSP00000327767.4
	ANO10	ENST00000414522.6	TSL:2	c.1808G>A	p.Cys603Tyr	missense	Exon 12 of 13	ENSP00000396990.2

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 695 AN: 152216 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000756 AC: 97 AN: 128366 AF XY: 0.000697

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.000534

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000479 AC: 662 AN: 1383050 Hom.: 4 Cov.: 32 AF XY: 0.000419 AC XY: 286 AN XY: 682374

African (AFR) AF: 0.0178 AC: 563 AN: 31586

American (AMR) AF: 0.000869 AC: 31 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.0000505 AC: 4 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33466

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5690

European-Non Finnish (NFE) AF: 0.00000927 AC: 10 AN: 1078602

Other (OTH) AF: 0.000881 AC: 51 AN: 57886

GnomAD4 genome AF: 0.00460 AC: 701 AN: 152334 Hom.: 3 Cov.: 33 AF XY: 0.00420 AC XY: 313 AN XY: 74486

African (AFR) AF: 0.0162 AC: 674 AN: 41576

American (AMR) AF: 0.00157 AC: 24 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00244 Hom.: 1

Bravo AF: 0.00560

ExAC AF: 0.000207 AC: 3

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.2
DANN	Benign	0.75
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.3
PROVEAN	Benign	0.35	N
REVEL	Benign	0.12
Sift	Benign	0.23	T
Sift4G	Benign	0.76	T
Vest4		0.17
MVP		0.24
ClinPred		0.0076	T
GERP RS		2.0
Mutation Taster		=98/2	polymorphism

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: rs141400669; hg19: chr3-43414329;