1-109483978-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001350175.2(ATXN7L2):c.25G>A(p.Ala9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN7L2 NM_001350175.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34

Genes affected

ATXN7L2 (HGNC:28713): (ataxin 7 like 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12775502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN7L2	NM_001350175.2	c.25G>A	p.Ala9Thr	missense_variant	1/11	ENST00000683729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN7L2	ENST00000683729.1	c.25G>A	p.Ala9Thr	missense_variant	1/11		NM_001350175.2	P2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.25e-7 AC: 1 AN: 1211416 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 590814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2023

The c.25G>A (p.A9T) alteration is located in exon 1 (coding exon 1) of the ATXN7L2 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the alanine (A) at amino acid position 9 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.52	N
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.034
Sift	Benign	0.24	T
Sift4G	Benign	0.30	T
Polyphen		0.14	B
Vest4		0.35
MutPred		0.23		Gain of glycosylation at A9 (P = 0.0553);
MVP		0.082
MPC		0.29
ClinPred		0.45	T
GERP RS		3.6
Varity_R		0.12
gMVP		0.45

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-110026600; COSMIC: COSV63994517; COSMIC: COSV63994517;