16-89984281-G-T

Variant names:

• chr16-89984281-G-T
• rs4238833
• ENST00000388970.8:n.649-250G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000388970.8(AFG3L1P):​n.649-250G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,970 control chromosomes in the GnomAD database, including 28,694 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 0.61 (28694 hom., cov: 32)
• Consequence: AFG3L1P ENST00000388970.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 30 publications found

Genes affected

AFG3L1P (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG3L1P	NR_003226.1	n.700-250G>T		intron_variant	Intron 5 of 10
AFG3L1P	NR_003227.1	n.627-250G>T		intron_variant	Intron 5 of 9
AFG3L1P	NR_003228.1	n.666-250G>T		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFG3L1P	ENST00000388970.8	n.649-250G>T		intron_variant	Intron 5 of 12	1
AFG3L1P	ENST00000421164.5	n.1538-250G>T		intron_variant	Intron 5 of 5	1
AFG3L1P	ENST00000421780.6	n.588-250G>T		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91973 AN: 151852 Hom.: 28666 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.606 AC: 92037 AN: 151970 Hom.: 28694 Cov.: 32 AF XY: 0.617 AC XY: 45805 AN XY: 74282

African (AFR) AF: 0.438 AC: 18143 AN: 41390

American (AMR) AF: 0.744 AC: 11358 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3468

East Asian (EAS) AF: 0.730 AC: 3770 AN: 5162

South Asian (SAS) AF: 0.707 AC: 3400 AN: 4808

European-Finnish (FIN) AF: 0.737 AC: 7796 AN: 10578

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43263 AN: 67976

Other (OTH) AF: 0.648 AC: 1367 AN: 2110

Alfa AF: 0.630 Hom.: 54749

Bravo AF: 0.597

Asia WGS AF: 0.713 AC: 2476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs4238833; hg19: chr16-90050689;