7-105614066-G-T

Position:

• chr7-105614066-G-T

Variant summary

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

The NM_020725.2(ATXN7L1):​c.2268C>A​(p.Asp756Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

Genes affected

ATXN7L1 (HGNC:22210): (ataxin 7 like 1)

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=0.097885996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.2268C>A	p.Asp756Glu	missense_variant	10/12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.2268C>A	p.Asp756Glu	missense_variant	10/12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1896C>A	p.Asp632Glu	missense_variant	8/10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1620C>A	p.Asp540Glu	missense_variant	10/10		NP_001305158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8	c.2268C>A	p.Asp756Glu	missense_variant	10/12	1	NM_020725.2	ENSP00000410759	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Nov 27, 2023

The c.2268C>A (p.D756E) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a C to A substitution at nucleotide position 2268, causing the aspartic acid (D) at amino acid position 756 to be replaced by a glutamic acid (E). 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	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.49
DEOGEN2	Benign	0.00077	T;.;T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;.;.;.
MutationTaster	Benign	0.52	D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.19	N;N;N;N
REVEL	Benign	0.064
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0050	B;B;.;.
Vest4		0.15
MutPred		0.097		Loss of loop (P = 0.0603);.;.;.;
MVP		0.45
MPC		0.39
ClinPred		0.66	D
GERP RS		4.3
Varity_R		0.074
gMVP		0.20

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: chr7-105254513;