rs8097342

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006796.3(AFG3L2):c.752+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,611,922 control chromosomes in the GnomAD database, including 465,812 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36461 hom., cov: 31)

Exomes 𝑓: 0.76 ( 429351 hom. )

Consequence

AFG3L2
NM_006796.3 splice_region, intron

Scores

Splicing: ADA: 0.00002846

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.246

Variant links:

Genes affected

AFG3L2 (HGNC:315): (AFG3 like matrix AAA peptidase subunit 2) This gene encodes a protein localized in mitochondria and closely related to paraplegin. The paraplegin gene is responsible for an autosomal recessive form of hereditary spastic paraplegia. This gene is a candidate gene for other hereditary spastic paraplegias or neurodegenerative disorders. [provided by RefSeq, Jul 2008]

AFG3L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-12359921-G-A is Benign according to our data. Variant chr18-12359921-G-A is described in ClinVar as [Benign]. Clinvar id is 136312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-12359921-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG3L2	NM_006796.3 link	c.752+6C>T		splice_region_variant, intron_variant	Intron 7 of 16	ENST00000269143.8	NP_006787.2	Q9Y4W6Q8TA92
AFG3L2	XM_011525601.4 link	c.752+6C>T		splice_region_variant, intron_variant	Intron 7 of 15		XP_011523903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFG3L2	ENST00000269143.8 link	c.752+6C>T		splice_region_variant, intron_variant	Intron 7 of 16	1	NM_006796.3	ENSP00000269143.2		Q9Y4W6

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103331

AN:

151832

Hom.:

36443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.713

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.681

GnomAD3 exomes

AF:

0.714

AC:

179613

AN:

251392

Hom.:

65553

AF XY:

0.726

AC XY:

98628

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.556

Gnomad ASJ exome

AF:

0.743

Gnomad EAS exome

AF:

0.606

Gnomad SAS exome

AF:

0.771

Gnomad FIN exome

AF:

0.810

Gnomad NFE exome

AF:

0.777

Gnomad OTH exome

AF:

0.725

GnomAD4 exome

AF:

0.764

AC:

1114860

AN:

1459972

Hom.:

429351

Cov.:

AF XY:

0.765

AC XY:

555322

AN XY:

726352

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.565

Gnomad4 ASJ exome

AF:

0.749

Gnomad4 EAS exome

AF:

0.592

Gnomad4 SAS exome

AF:

0.772

Gnomad4 FIN exome

AF:

0.808

Gnomad4 NFE exome

AF:

0.785

Gnomad4 OTH exome

AF:

0.746

GnomAD4 genome

AF:

0.680

AC:

103374

AN:

151950

Hom.:

36461

Cov.:

AF XY:

0.682

AC XY:

50655

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.745

Gnomad4 EAS

AF:

0.615

Gnomad4 SAS

AF:

0.768

Gnomad4 FIN

AF:

0.817

Gnomad4 NFE

AF:

0.780

Gnomad4 OTH

AF:

0.683

Alfa

AF:

0.732

Hom.:

18251

Bravo

AF:

0.654

Asia WGS

AF:

0.655

AC:

2274

AN:

3478

EpiCase

AF:

0.766

EpiControl

AF:

0.763

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 09, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 21, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Feb 11, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 12, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Spinocerebellar ataxia type 28

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spastic ataxia 5

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Optic atrophy 12

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.8

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over