2-86173701-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IMMT NM_006839.3 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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMT	NM_006839.3	c.370C>A	p.Pro124Thr	missense_variant	Exon 4 of 15	ENST00000410111.8	NP_006830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMT	ENST00000410111.8	c.370C>A	p.Pro124Thr	missense_variant	Exon 4 of 15	1	NM_006839.3	ENSP00000387262.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;D;D;D;D;.
Sift4G	Benign	0.089	T;T;T;T;T;D
Polyphen		1.0, 1.0, 0.99	.;D;D;.;D;.
Vest4		0.48
MutPred		0.52		.;Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);Gain of MoRF binding (P = 0.0425);
MVP		0.50
MPC		0.52
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.21
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-86400824;