7-105614667-T-C

Variant names:

• chr7-105614667-T-C
• NM_020725.2:c.1667A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020725.2(ATXN7L1):​c.1667A>G​(p.Tyr556Cys) 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: 4.82

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38376468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.1667A>G	p.Tyr556Cys	missense_variant	Exon 10 of 12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.1667A>G	p.Tyr556Cys	missense_variant	Exon 10 of 12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1295A>G	p.Tyr432Cys	missense_variant	Exon 8 of 10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1019A>G	p.Tyr340Cys	missense_variant	Exon 10 of 10		NP_001305158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8	c.1667A>G	p.Tyr556Cys	missense_variant	Exon 10 of 12	1	NM_020725.2	ENSP00000410759.3

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

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1667A>G (p.Y556C) 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 1667, causing the tyrosine (Y) at amino acid position 556 to be replaced by a cysteine (C). 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	0.086
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T;.;T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.64	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.19	T;T;D;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		1.0	D;D;.;.
Vest4		0.67
MutPred		0.38		Gain of loop (P = 0.0079);.;.;.;
MVP		0.83
MPC		1.4
ClinPred		0.57	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.55

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: chr7-105255114;