2-86173701-G-C

Variant names:

• chr2-86173701-G-C
• rs1050301
• NM_006839.3:c.370C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006839.3(IMMT):​c.370C>G​(p.Pro124Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: IMMT NM_006839.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14
• Publications: 41 publications found

Genes affected

IMMT (HGNC:6047): (inner membrane mitochondrial protein) Enables RNA binding activity. Involved in cristae formation. Located in mitochondrial inner membrane. Part of MICOS complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24557585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006839.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMT	NM_006839.3	MANE Select	c.370C>G	p.Pro124Ala	missense	Exon 4 of 15	NP_006830.2
	IMMT	NM_001100169.2		c.370C>G	p.Pro124Ala	missense	Exon 4 of 15	NP_001093639.1
	IMMT	NM_001400086.1		c.370C>G	p.Pro124Ala	missense	Exon 4 of 15	NP_001387015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMT	ENST00000410111.8	TSL:1 MANE Select	c.370C>G	p.Pro124Ala	missense	Exon 4 of 15	ENSP00000387262.3
	IMMT	ENST00000442664.6	TSL:1	c.370C>G	p.Pro124Ala	missense	Exon 4 of 15	ENSP00000407788.2
	IMMT	ENST00000449247.6	TSL:1	c.370C>G	p.Pro124Ala	missense	Exon 4 of 15	ENSP00000396899.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.92	T
PhyloP100		6.1
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Benign	0.36	T
Polyphen		0.99	D
Vest4		0.38
MutPred		0.49		Loss of helix (P = 0.0104)
MVP		0.44
MPC		0.52
ClinPred		0.98	D
GERP RS		3.4
PromoterAI		-0.0029	Neutral
Varity_R		0.11
gMVP		0.42
Mutation Taster		=75/25	polymorphism

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: rs1050301; hg19: chr2-86400824;