7-105613910-G-C

Variant names:

• chr7-105613910-G-C
• NM_020725.2:c.2424C>G
• ATXN7L1 p.Ser808Arg

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.2424C>G​(p.Ser808Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91
• 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=0.1992718).

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.2424C>G	p.Ser808Arg	missense	Exon 10 of 12	NP_065776.1	Q9ULK2-1
	ATXN7L1	NM_001385596.1		c.2424C>G	p.Ser808Arg	missense	Exon 10 of 12	NP_001372525.1
	ATXN7L1	NM_138495.2		c.2052C>G	p.Ser684Arg	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.2424C>G	p.Ser808Arg	missense	Exon 10 of 12	ENSP00000410759.3	Q9ULK2-1
	ATXN7L1	ENST00000484475.5	TSL:1	c.1527C>G	p.Ser509Arg	missense	Exon 4 of 4	ENSP00000418900.1	H0Y8A2
	ATXN7L1	ENST00000474433.5	TSL:1	n.*1999C>G		non_coding_transcript_exon	Exon 9 of 9	ENSP00000420483.1	F8WDE7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0078	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.036
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0090	D
Varity_R		0.25
gMVP		0.46
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-105254357;