7-105613942-T-C

Position:

• chr7-105613942-T-C

Variant summary

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

The NM_020725.2(ATXN7L1):​c.2392A>G​(p.Met798Val) variant causes a missense change. 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: 32)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44

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=0.21065491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.2392A>G	p.Met798Val	missense_variant	10/12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.2392A>G	p.Met798Val	missense_variant	10/12		NP_001372525.1
ATXN7L1	NM_138495.2	c.2020A>G	p.Met674Val	missense_variant	8/10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1744A>G	p.Met582Val	missense_variant	10/10		NP_001305158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8	c.2392A>G	p.Met798Val	missense_variant	10/12	1	NM_020725.2	ENSP00000410759.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 07, 2023

The c.2392A>G (p.M798V) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a A to G substitution at nucleotide position 2392, causing the methionine (M) at amino acid position 798 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0018	T;.;T;T
Eigen	Benign	0.035
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.10	N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.43	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.25	B;P;.;.
Vest4		0.55
MutPred		0.17		Loss of MoRF binding (P = 0.1057);.;.;.;
MVP		0.65
MPC		0.98
ClinPred		0.52	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.21

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: chr7-105254389;