NM_006839.3:c.1785A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate 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
• Publications: 19 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.137).
• 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.

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.1785A>G	p.Ala595Ala	synonymous	Exon 15 of 15	NP_006830.2	Q16891-1
	IMMT	NM_001100169.2		c.1782A>G	p.Ala594Ala	synonymous	Exon 15 of 15	NP_001093639.1	Q16891-4
	IMMT	NM_001400086.1		c.1779A>G	p.Ala593Ala	synonymous	Exon 15 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.1785A>G	p.Ala595Ala	synonymous	Exon 15 of 15	ENSP00000387262.3	Q16891-1
	IMMT	ENST00000442664.6	TSL:1	c.1782A>G	p.Ala594Ala	synonymous	Exon 15 of 15	ENSP00000407788.2	Q16891-4
	IMMT	ENST00000449247.6	TSL:1	c.1752A>G	p.Ala584Ala	synonymous	Exon 15 of 15	ENSP00000396899.2	Q16891-2

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

GnomAD2 exomes AF: 0.420 AC: 104703 AN: 249196 AF XY: 0.427

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 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

African (AFR) AF: 0.102 AC: 3414 AN: 33470

American (AMR) AF: 0.395 AC: 17681 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12375 AN: 26136

East Asian (EAS) AF: 0.161 AC: 6398 AN: 39686

South Asian (SAS) AF: 0.380 AC: 32808 AN: 86240

European-Finnish (FIN) AF: 0.500 AC: 26708 AN: 53396

Middle Eastern (MID) AF: 0.408 AC: 2280 AN: 5582

European-Non Finnish (NFE) AF: 0.506 AC: 562932 AN: 1111764

Other (OTH) AF: 0.444 AC: 26820 AN: 60348

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

African (AFR) AF: 0.115 AC: 4764 AN: 41512

American (AMR) AF: 0.398 AC: 6070 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3468

East Asian (EAS) AF: 0.150 AC: 776 AN: 5174

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4820

European-Finnish (FIN) AF: 0.487 AC: 5155 AN: 10582

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34777 AN: 67954

Other (OTH) AF: 0.393 AC: 830 AN: 2112

Alfa AF: 0.459 Hom.: 9625

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.47
PhyloP100		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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