NM_020725.2:c.2348C>G

Variant names:

• chr7-105613986-G-C
• NM_020725.2:c.2348C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020725.2(ATXN7L1):​c.2348C>G​(p.Ser783Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.38

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.2348C>G	p.Ser783Trp	missense_variant	Exon 10 of 12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.2348C>G	p.Ser783Trp	missense_variant	Exon 10 of 12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1976C>G	p.Ser659Trp	missense_variant	Exon 8 of 10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1700C>G	p.Ser567Trp	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.2348C>G	p.Ser783Trp	missense_variant	Exon 10 of 12	1	NM_020725.2	ENSP00000410759.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399900 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690426

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2348C>G (p.S783W) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a C to G substitution at nucleotide position 2348, causing the serine (S) at amino acid position 783 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.55
MutPred		0.24		Loss of phosphorylation at S783 (P = 0.0011);.;.;.;
MVP		0.92
MPC		1.5
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.49
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-105254433;