dbSNP rs73283859: AFG3L1P: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 ENST00000418696.5(AFG3L1P):n.2451G>C variant causes a non coding transcript exon 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
ENST00000418696.5 non_coding_transcript_exon

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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new If you want to explore the variant's impact on the transcript ENST00000418696.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418696.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
AFG3L1P	NR_003226.1	n.2660G>C	non_coding_transcript_exon	Exon 11 of 11
AFG3L1P	NR_003227.1	n.2421G>C	non_coding_transcript_exon	Exon 10 of 10
AFG3L1P	NR_003228.1	n.1206+2219G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
AFG3L1P	ENST00000355531.7	TSL:1	n.828+2219G>C	intron	N/A
AFG3L1P	ENST00000388970.8	TSL:1	n.1189+2219G>C	intron	N/A
AFG3L1P	ENST00000418696.5	TSL:2	n.2451G>C	non_coding_transcript_exon	Exon 9 of 9

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over