7-105614665-T-G

Variant names:

• chr7-105614665-T-G
• rs561281717
• NM_020725.2:c.1669A>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.1669A>C​(p.Ile557Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43

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=0.09894997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.1669A>C	p.Ile557Leu	missense_variant	Exon 10 of 12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.1669A>C	p.Ile557Leu	missense_variant	Exon 10 of 12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1297A>C	p.Ile433Leu	missense_variant	Exon 8 of 10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1021A>C	p.Ile341Leu	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.1669A>C	p.Ile557Leu	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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.0018	T;.;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.099	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.14	N;N;N;N
REVEL	Benign	0.042
Sift	Benign	0.67	T;T;T;T
Sift4G	Benign	0.66	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.24
MutPred		0.28		Gain of loop (P = 0.0045);.;.;.;
MVP		0.38
MPC		0.40
ClinPred		0.65	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs561281717; hg19: chr7-105255112;