chr2-86173701-G-C

Position:

• chr2-86173701-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000410111.8(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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P124S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IMMT ENST00000410111.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMT	NM_006839.3	c.370C>G	p.Pro124Ala	missense_variant	4/15	ENST00000410111.8	NP_006830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMMT	ENST00000410111.8	c.370C>G	p.Pro124Ala	missense_variant	4/15	1	NM_006839.3	ENSP00000387262	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;T;T;T;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;.
REVEL	Benign	0.17
Sift	Uncertain	0.011	D;T;D;D;T;.
Sift4G	Benign	0.36	T;T;T;T;T;D
Polyphen		0.99, 0.99, 0.94	.;D;D;.;P;.
Vest4		0.38
MutPred		0.49		.;Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP		0.44
MPC		0.52
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs1050301; hg19: chr2-86400824;