rs1312557744

Variant names:

• chr7-105614441-G-T
• rs1312557744
• NM_020725.2:c.1893C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-105614441-G-T
• chr7-105614441-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020725.2(ATXN7L1):​c.1893C>A​(p.Asp631Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,545,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D631H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69
• Publications: 0 publications found

Genes affected

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

ENSG00000295921 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18445364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020725.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN7L1	NM_020725.2	MANE Select	c.1893C>A	p.Asp631Glu	missense	Exon 10 of 12	NP_065776.1	Q9ULK2-1
	ATXN7L1	NM_001385596.1		c.1893C>A	p.Asp631Glu	missense	Exon 10 of 12	NP_001372525.1
	ATXN7L1	NM_138495.2		c.1521C>A	p.Asp507Glu	missense	Exon 8 of 10	NP_612504.1	Q9ULK2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN7L1	ENST00000419735.8	TSL:1 MANE Select	c.1893C>A	p.Asp631Glu	missense	Exon 10 of 12	ENSP00000410759.3	Q9ULK2-1
	ATXN7L1	ENST00000484475.5	TSL:1	c.996C>A	p.Asp332Glu	missense	Exon 4 of 4	ENSP00000418900.1	H0Y8A2
	ATXN7L1	ENST00000474433.5	TSL:1	n.*1468C>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000420483.1	F8WDE7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152140 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000647 AC: 1 AN: 154530 AF XY: 0.0000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000165 AC: 23 AN: 1393260 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 17 AN XY: 686426

African (AFR) AF: 0.00 AC: 0 AN: 31176

American (AMR) AF: 0.00 AC: 0 AN: 34762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24748

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.0000762 AC: 6 AN: 78734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.0000112 AC: 12 AN: 1075324

Other (OTH) AF: 0.0000865 AC: 5 AN: 57812

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.59
DEOGEN2	Benign	0.0021	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N
PhyloP100		2.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.24
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.98	D
Vest4		0.35
MutPred		0.37		Gain of sheet (P = 0.0101)
MVP		0.61
MPC		0.74
ClinPred		0.24	T
GERP RS		5.7
Varity_R		0.12
gMVP		0.27
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1312557744; hg19: chr7-105254888;