7-105614517-G-C

Variant names:

• chr7-105614517-G-C
• rs778680974
• NM_020725.2:c.1817C>G

Variant summary

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

The NM_020725.2(ATXN7L1):​c.1817C>G​(p.Pro606Arg) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATXN7L1 NM_020725.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.63

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=0.24356493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L1	NM_020725.2	c.1817C>G	p.Pro606Arg	missense_variant	Exon 10 of 12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1	c.1817C>G	p.Pro606Arg	missense_variant	Exon 10 of 12		NP_001372525.1
ATXN7L1	NM_138495.2	c.1445C>G	p.Pro482Arg	missense_variant	Exon 8 of 10		NP_612504.1
ATXN7L1	NM_001318229.2	c.1169C>G	p.Pro390Arg	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.1817C>G	p.Pro606Arg	missense_variant	Exon 10 of 12	1	NM_020725.2	ENSP00000410759.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000138 AC: 2 AN: 144618 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74984

Gnomad AFR exome AF: 0.000243

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000682 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.66	P;P;.;.
Vest4		0.42
MutPred		0.43		Gain of MoRF binding (P = 0.0346);.;.;.;
MVP		0.63
MPC		0.86
ClinPred		0.47	T
GERP RS		5.7
Varity_R		0.37
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs778680974; hg19: chr7-105254964;