7-105610533-C-G

Variant names:

• chr7-105610533-C-G
• rs182409100
• NM_020725.2:c.2543G>C

Variant summary

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

The NM_020725.2(ATXN7L1):​c.2543G>C​(p.Arg848Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,660 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R848Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12
• Publications: 0 publications found

Genes affected

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

ENSG00000295921 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2543G>C	p.Arg848Pro	missense	Exon 11 of 12	NP_065776.1	Q9ULK2-1
	ATXN7L1	NM_001385596.1		c.2543G>C	p.Arg848Pro	missense	Exon 11 of 12	NP_001372525.1
	ATXN7L1	NM_138495.2		c.2171G>C	p.Arg724Pro	missense	Exon 9 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.2543G>C	p.Arg848Pro	missense	Exon 11 of 12	ENSP00000410759.3	Q9ULK2-1
	ATXN7L1	ENST00000477775.5	TSL:2	c.2171G>C	p.Arg724Pro	missense	Exon 9 of 10	ENSP00000418476.1	Q9ULK2-3
	ENSG00000295921	ENST00000733939.1		n.109-27199C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398660 Hom.: 0 Cov.: 34 AF XY: 0.00000145 AC XY: 1 AN XY: 689870

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31576

American (AMR) AF: 0.00 AC: 0 AN: 35610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 79160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078502

Other (OTH) AF: 0.00 AC: 0 AN: 57968

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0019	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0086	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.22
Sift	Uncertain	0.016	D
Sift4G	Benign	0.17	T
Polyphen		0.97	D
Vest4		0.70
MutPred		0.14		Loss of MoRF binding (P = 0.012)
MVP		0.59
MPC		0.91
ClinPred		0.70	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.71
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs182409100; hg19: chr7-105250980;