17-44197308-G-C

Position:

• chr17-44197308-G-C

Variant summary

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

The NM_001382309.1(ATXN7L3):​c.276C>G​(p.Ser92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ATXN7L3 NM_001382309.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

Genes affected

ATXN7L3 (HGNC:25416): (ataxin 7 like 3) Enables nuclear receptor coactivator activity. Involved in histone deubiquitination; histone monoubiquitination; and positive regulation of transcription, DNA-templated. Located in nucleus. Part of DUBm complex and SAGA complex. [provided by Alliance of Genome Resources, Apr 2022]

ATXN7L3 (HGNC:):

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=0.23590112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7L3	NM_001382309.1	c.276C>G	p.Ser92Arg	missense_variant	4/13	ENST00000587097.6	NP_001369238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7L3	ENST00000587097.6	c.276C>G	p.Ser92Arg	missense_variant	4/13	5	NM_001382309.1	ENSP00000465614.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Hadassah Hebrew University Medical Center

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N;N;.;.;.
REVEL	Benign	0.10
Sift	Benign	0.18	T;T;.;.;.
Sift4G	Benign	0.48	T;T;T;.;.
Polyphen		0.99	D;D;.;.;.
Vest4		0.55
MutPred		0.24		Gain of catalytic residue at S92 (P = 0.0062);Gain of catalytic residue at S92 (P = 0.0062);Gain of catalytic residue at S92 (P = 0.0062);Gain of catalytic residue at S92 (P = 0.0062);Gain of catalytic residue at S92 (P = 0.0062);
MVP		0.28
MPC		2.0
ClinPred		0.57	D
GERP RS		2.6
Varity_R		0.12
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: chr17-42274676;