7-105614665-T-C

Variant names:

• chr7-105614665-T-C
• rs561281717
• NM_020725.2:c.1669A>G

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>G​(p.Ile557Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,551,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• 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=0.0714573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.1669A>G	p.Ile557Val	missense_variant	Exon 10 of 12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.1669A>G	p.Ile557Val	missense_variant	Exon 10 of 12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1297A>G	p.Ile433Val	missense_variant	Exon 8 of 10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1021A>G	p.Ile341Val	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>G	p.Ile557Val	missense_variant	Exon 10 of 12	1	NM_020725.2	ENSP00000410759.3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399496 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690264

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: 0.0000203

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74394

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.00051	T;.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.023
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.071	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.010	N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.82	T;T;D;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.070	B;B;.;.
Vest4		0.25
MutPred		0.29		Loss of helix (P = 0.0123);.;.;.;
MVP		0.55
MPC		0.40
ClinPred		0.33	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.33

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;