NM_020725.2:c.2543G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.2543G>C	p.Arg848Pro	missense_variant	Exon 11 of 12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.2543G>C	p.Arg848Pro	missense_variant	Exon 11 of 12		NP_001372525.1
ATXN7L1	NM_138495.2	c.2171G>C	p.Arg724Pro	missense_variant	Exon 9 of 10		NP_612504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8	c.2543G>C	p.Arg848Pro	missense_variant	Exon 11 of 12	1	NM_020725.2	ENSP00000410759.3
ATXN7L1	ENST00000477775.5	c.2171G>C	p.Arg724Pro	missense_variant	Exon 9 of 10	2		ENSP00000418476.1

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

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: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0086	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.016	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.97	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-105250980;