Genetic Variant ENST00000355531.7:n.828+2219G>C (chr16-89996112-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000355531.7(AFG3L1P):n.828+2219G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 174,492 control chromosomes in the GnomAD database, including 313 homozygotes. 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: 𝑓 0.056 ( 285 hom., cov: 33)

Exomes 𝑓: 0.041 ( 28 hom. )

Consequence

AFG3L1P
ENST00000355531.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0350

Publications

14 publications found

Variant links:

Genes affected

AFG3L1P (HGNC:):

AFG3L1P links:

AFG3L1P (HGNC:314): (AFG3 like matrix AAA peptidase subunit 1, pseudogene) Predicted to be involved in protein processing. Predicted to act upstream of or within cristae formation; mitochondrial fusion; and mitochondrial protein processing. Predicted to be located in mitochondrial inner membrane. Predicted to be part of m-AAA complex. [provided by Alliance of Genome Resources, Apr 2022]

AFG3L1P links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
AFG3L1P	NR_003226.1 link	n.2660G>C	non_coding_transcript_exon_variant	Exon 11 of 11
AFG3L1P	NR_003227.1 link	n.2421G>C	non_coding_transcript_exon_variant	Exon 10 of 10
AFG3L1P	NR_003228.1 link	n.1206+2219G>C	intron_variant	Intron 10 of 12

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
AFG3L1P	ENST00000355531.7 link	n.828+2219G>C	intron_variant	Intron 4 of 6	1
AFG3L1P	ENST00000388970.8 link	n.1189+2219G>C	intron_variant	Intron 10 of 12	1
AFG3L1P	ENST00000418696.5 link	n.2451G>C	non_coding_transcript_exon_variant	Exon 9 of 9	2

Frequencies

GnomAD3 genomes

AF:

0.0556

AC:

8469

AN:

152198

Hom.:

285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.0749

Gnomad EAS

AF:

0.00577

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0581

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0705

Gnomad OTH

AF:

0.0344

GnomAD4 exome

AF:

0.0407

AC:

903

AN:

22176

Hom.:

Cov.:

AF XY:

0.0337

AC XY:

443

AN XY:

13148

show subpopulations

African (AFR)

AF:

0.0563

AC:

AN:

160

American (AMR)

AF:

0.0190

AC:

AN:

210

Ashkenazi Jewish (ASJ)

AF:

0.0515

AC:

AN:

524

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00679

AC:

AN:

7068

European-Finnish (FIN)

AF:

0.0367

AC:

AN:

1064

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0609

AC:

724

AN:

11896

Other (OTH)

AF:

0.0470

AC:

AN:

1064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0556

AC:

8469

AN:

152316

Hom.:

285

Cov.:

AF XY:

0.0526

AC XY:

3918

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0556

AC:

2310

AN:

41560

American (AMR)

AF:

0.0188

AC:

288

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0749

AC:

260

AN:

3470

East Asian (EAS)

AF:

0.00578

AC:

AN:

5190

South Asian (SAS)

AF:

0.00911

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0581

AC:

617

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0705

AC:

4798

AN:

68022

Other (OTH)

AF:

0.0340

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

423

846

1270

1693

2116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0633

Hom.:

Bravo

AF:

0.0544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.7

(source)

DANN

Benign

0.51

PhyloP100

-0.035

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over