rs10499999

Variant names:

• chr7-110769305-C-T
• rs10499999
• NM_032549.4:c.409-105584G>A

Variant summary

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

The NM_032549.4(IMMP2L):​c.409-105584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,054 control chromosomes in the GnomAD database, including 7,954 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 0.32 (7954 hom., cov: 32)
• Consequence: IMMP2L NM_032549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 7 publications found

Genes affected

IMMP2L (HGNC:14598): (inner mitochondrial membrane peptidase subunit 2) This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMP2L	NM_032549.4	c.409-105584G>A		intron_variant	Intron 5 of 5	ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMP2L	ENST00000405709.7	c.409-105584G>A		intron_variant	Intron 5 of 5	1	NM_032549.4	ENSP00000384966.2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48454 AN: 151938 Hom.: 7955 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.0959

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.319 AC: 48476 AN: 152054 Hom.: 7954 Cov.: 32 AF XY: 0.316 AC XY: 23450 AN XY: 74318

African (AFR) AF: 0.281 AC: 11664 AN: 41494

American (AMR) AF: 0.326 AC: 4971 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3466

East Asian (EAS) AF: 0.0953 AC: 493 AN: 5172

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4828

European-Finnish (FIN) AF: 0.334 AC: 3527 AN: 10556

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24387 AN: 67970

Other (OTH) AF: 0.325 AC: 687 AN: 2112

Alfa AF: 0.346 Hom.: 15792

Bravo AF: 0.316

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.5
DANN	Benign	0.72
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10499999; hg19: chr7-110409361;