2-86144760-T-C

Variant names:

• chr2-86144760-T-C
• rs8244
• NM_006839.3:c.1785A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006839.3(IMMT):​c.1785A>G​(p.Ala595Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,613,432 control chromosomes in the GnomAD database, including 182,782 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 0.37 (12895 hom., cov: 32)
  • Exomes 𝑓: 0.47 (169887 hom.)
• Consequence: IMMT NM_006839.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.25

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-5.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMT	NM_006839.3	c.1785A>G	p.Ala595Ala	synonymous_variant	Exon 15 of 15	ENST00000410111.8	NP_006830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMT	ENST00000410111.8	c.1785A>G	p.Ala595Ala	synonymous_variant	Exon 15 of 15	1	NM_006839.3	ENSP00000387262.3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56459 AN: 151974 Hom.: 12900 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.395

GnomAD3 exomes AF: 0.420 AC: 104703 AN: 249196 Hom.: 24160 AF XY: 0.427 AC XY: 57704 AN XY: 135180

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.374

Gnomad FIN exome AF: 0.502

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.473 AC: 691416 AN: 1461340 Hom.: 169887 Cov.: 56 AF XY: 0.472 AC XY: 343123 AN XY: 726960

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.371 AC: 56447 AN: 152092 Hom.: 12895 Cov.: 32 AF XY: 0.369 AC XY: 27471 AN XY: 74348

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.393

Alfa AF: 0.468 Hom.: 6940

Bravo AF: 0.351

Asia WGS AF: 0.260 AC: 905 AN: 3478

EpiCase AF: 0.500

EpiControl AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs8244; hg19: chr2-86371883; COSMIC: COSV54480193; COSMIC: COSV54480193;