rs761335657

Variant names:

• chr7-105614155-C-A
• rs761335657
• NM_020725.2:c.2179G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-105614155-C-A
• chr7-105614155-C-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.2179G>T​(p.Ala727Ser) 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 1,551,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: -0.250

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=0.06847912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.2179G>T	p.Ala727Ser	missense_variant	Exon 10 of 12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.2179G>T	p.Ala727Ser	missense_variant	Exon 10 of 12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1807G>T	p.Ala603Ser	missense_variant	Exon 8 of 10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1531G>T	p.Ala511Ser	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.2179G>T	p.Ala727Ser	missense_variant	Exon 10 of 12	1	NM_020725.2	ENSP00000410759.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 1399332 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690156

Gnomad4 AFR exome AF: 0.0000633

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0065	T;.;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.85	D;D;D;D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.25	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.086	T;T;T;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.13
MutPred		0.23		Gain of glycosylation at A727 (P = 0.0317);.;.;.;
MVP		0.40
MPC		0.39
ClinPred		0.076	T
GERP RS		-3.5
Varity_R		0.077
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761335657; hg19: chr7-105254602;