16-89984281-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_003228.1(AFG3L1P):n.666-250G>T variant causes a intron, non coding transcript 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 NR_003228.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

Genes affected

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AFG3L1P	NR_003228.1	n.666-250G>T		intron_variant, non_coding_transcript_variant
AFG3L1P	NR_003226.1	n.700-250G>T		intron_variant, non_coding_transcript_variant
AFG3L1P	NR_003227.1	n.627-250G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG3L1P	ENST00000418696.5	n.591-250G>T		intron_variant, non_coding_transcript_variant		2
AFG3L1P	ENST00000557444.5	n.615-250G>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.648

Alfa AF: 0.635 Hom.: 39465

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4238833; hg19: chr16-90050689;