16-28823371-C-T

Variant names:

• chr16-28823371-C-T
• rs1396513310
• NM_007245.4:c.112C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007245.4(ATXN2L):​c.112C>T​(p.Leu38Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN2L NM_007245.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 0 publications found

Genes affected

ATXN2L (HGNC:31326): (ataxin 2 like) This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000275807 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2073276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007245.4. 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
	ATXN2L	NM_007245.4	MANE Select	c.112C>T	p.Leu38Phe	missense	Exon 1 of 22	NP_009176.2
	ATXN2L	NM_001387166.1		c.112C>T	p.Leu38Phe	missense	Exon 1 of 24	NP_001374095.1
	ATXN2L	NM_001387167.1		c.112C>T	p.Leu38Phe	missense	Exon 1 of 24	NP_001374096.1	Q8WWM7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN2L	ENST00000336783.9	TSL:1 MANE Select	c.112C>T	p.Leu38Phe	missense	Exon 1 of 22	ENSP00000338718.4	Q8WWM7-1
	ATXN2L	ENST00000395547.6	TSL:1	c.112C>T	p.Leu38Phe	missense	Exon 1 of 24	ENSP00000378917.2	Q8WWM7-3
	ATXN2L	ENST00000564304.5	TSL:1	c.112C>T	p.Leu38Phe	missense	Exon 1 of 23	ENSP00000457613.1	H3BUF6

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1192978 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 579830

African (AFR) AF: 0.00 AC: 0 AN: 24664

American (AMR) AF: 0.00 AC: 0 AN: 16470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15902

East Asian (EAS) AF: 0.00 AC: 0 AN: 29952

South Asian (SAS) AF: 0.00 AC: 0 AN: 42460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 983274

Other (OTH) AF: 0.00 AC: 0 AN: 47766

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152020 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74260

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67936

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.079
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.057	T
Polyphen		0.99	D
Vest4		0.088
MutPred		0.13		Loss of glycosylation at P41 (P = 0.2269)
MVP		0.26
MPC		0.54
ClinPred		0.63	D
GERP RS		4.0
PromoterAI		-0.058	Neutral
Varity_R		0.23
gMVP		0.13

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: rs1396513310; hg19: chr16-28834692;