rs10258236

Variant names:

• chr7-111468204-T-C
• rs10258236
• NM_032549.4:c.239+19034A>G

Variant summary

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

The NM_032549.4(IMMP2L):​c.239+19034A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,096 control chromosomes in the GnomAD database, including 4,548 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 0.18 (4548 hom., cov: 32)
• Consequence: IMMP2L NM_032549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMP2L	NM_032549.4	c.239+19034A>G		intron_variant	Intron 3 of 5	ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMP2L	ENST00000405709.7	c.239+19034A>G		intron_variant	Intron 3 of 5	1	NM_032549.4	ENSP00000384966.2
IMMP2L	ENST00000331762.7	c.239+19034A>G		intron_variant	Intron 4 of 6	1		ENSP00000329553.3
IMMP2L	ENST00000452895.5	c.239+19034A>G		intron_variant	Intron 4 of 6	5		ENSP00000399353.1
IMMP2L	ENST00000447215.5	c.239+19034A>G		intron_variant	Intron 3 of 4	3		ENSP00000388327.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26981 AN: 151980 Hom.: 4515 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.178 AC: 27058 AN: 152096 Hom.: 4548 Cov.: 32 AF XY: 0.171 AC XY: 12704 AN XY: 74360

African (AFR) AF: 0.444 AC: 18377 AN: 41420

American (AMR) AF: 0.0980 AC: 1498 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4824

European-Finnish (FIN) AF: 0.0680 AC: 721 AN: 10608

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5516 AN: 67998

Other (OTH) AF: 0.167 AC: 352 AN: 2104

Alfa AF: 0.104 Hom.: 1669

Bravo AF: 0.194

Asia WGS AF: 0.0420 AC: 147 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.44
PhyloP100		-0.20
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: rs10258236; hg19: chr7-111108260;