2-86173701-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006839.3(IMMT):​c.370C>A​(p.Pro124Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IMMT NM_006839.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3036309).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMT	NM_006839.3	MANE Select	c.370C>A	p.Pro124Thr	missense	Exon 4 of 15	NP_006830.2	Q16891-1
	IMMT	NM_001100169.2		c.370C>A	p.Pro124Thr	missense	Exon 4 of 15	NP_001093639.1	Q16891-4
	IMMT	NM_001400086.1		c.370C>A	p.Pro124Thr	missense	Exon 4 of 15	NP_001387015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMT	ENST00000410111.8	TSL:1 MANE Select	c.370C>A	p.Pro124Thr	missense	Exon 4 of 15	ENSP00000387262.3	Q16891-1
	IMMT	ENST00000442664.6	TSL:1	c.370C>A	p.Pro124Thr	missense	Exon 4 of 15	ENSP00000407788.2	Q16891-4
	IMMT	ENST00000449247.6	TSL:1	c.370C>A	p.Pro124Thr	missense	Exon 4 of 15	ENSP00000396899.2	Q16891-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453728 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723542

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 85830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105098

Other (OTH) AF: 0.00 AC: 0 AN: 60088

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.86	T
PhyloP100		6.1
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.089	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.52		Gain of MoRF binding (P = 0.0425)
MVP		0.50
MPC		0.52
ClinPred		0.98	D
GERP RS		3.4
PromoterAI		-0.0010	Neutral
Varity_R		0.21
gMVP		0.50
Mutation Taster		=76/24	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;