rs73283859

chr16-89996112-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFG3L1P	NR_003228.1	n.1206+2219G>C		intron_variant, non_coding_transcript_variant
AFG3L1P	NR_003226.1	n.2660G>C		non_coding_transcript_exon_variant	11/11
AFG3L1P	NR_003227.1	n.2421G>C		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG3L1P	ENST00000418696.5	n.2451G>C		non_coding_transcript_exon_variant	9/9	2
AFG3L1P	ENST00000557444.5	n.1606-671G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8469 AN: 152198 Hom.: 285 Cov.: 33

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.: 28 Cov.: 0 AF XY: 0.0337 AC XY: 443 AN XY: 13148

Gnomad4 AFR exome AF: 0.0563

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0515

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00679

Gnomad4 FIN exome AF: 0.0367

Gnomad4 NFE exome AF: 0.0609

Gnomad4 OTH exome AF: 0.0470

GnomAD4 genome AF: 0.0556 AC: 8469 AN: 152316 Hom.: 285 Cov.: 33 AF XY: 0.0526 AC XY: 3918 AN XY: 74480

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.0581

Gnomad4 NFE AF: 0.0705

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0633 Hom.: 30

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
Dann	Benign	0.51
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

LitVar

Other links and lift over

dbSNP: rs73283859; hg19: chr16-90062520;