7-105614713-C-A

Position:

• chr7-105614713-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020725.2(ATXN7L1):​c.1621G>T​(p.Val541Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,399,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2599056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.1621G>T	p.Val541Leu	missense_variant	10/12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.1621G>T	p.Val541Leu	missense_variant	10/12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1249G>T	p.Val417Leu	missense_variant	8/10		NP_612504.1
ATXN7L1	NM_001318229.2	c.973G>T	p.Val325Leu	missense_variant	10/10		NP_001305158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8	c.1621G>T	p.Val541Leu	missense_variant	10/12	1	NM_020725.2	ENSP00000410759.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399480 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690242

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.0000689

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.1621G>T (p.V541L) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a G to T substitution at nucleotide position 1621, causing the valine (V) at amino acid position 541 to be replaced by a leucine (L). 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	Benign	0.17
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0049	T;.;T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.73	N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.48	T;T;D;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.69	P;P;.;.
Vest4		0.47
MutPred		0.11		Loss of phosphorylation at Y542 (P = 0.1305);.;.;.;
MVP		0.52
MPC		1.1
ClinPred		0.61	D
GERP RS		5.7
Varity_R		0.14
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-105255160;