chr22-30427078-G-A

Variant names:

• chr22-30427078-G-A
• rs2072159
• NM_016498.5:c.196-93G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016498.5(MTFP1):​c.196-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,450,784 control chromosomes in the GnomAD database, including 51,355 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 0.28 (6195 hom., cov: 32)
  • Exomes 𝑓: 0.26 (45160 hom.)
• Consequence: MTFP1 NM_016498.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 8 publications found

Genes affected

MTFP1 (HGNC:26945): (mitochondrial fission process 1) MTP18 is a mitochondrial protein and downstream target of the phosphatidylinositol 3-kinase (see PIK3CA, MIM 171834) signaling pathway that plays a role in cell viability and mitochondrial dynamics (Tondera et al., 2004 [PubMed 15155745]).[supplied by OMIM, Mar 2008]

ENSG00000249590 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016498.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFP1	NM_016498.5	MANE Select	c.196-93G>A		intron	N/A	NP_057582.2
	MTFP1	NM_001003704.3		c.195+234G>A		intron	N/A	NP_001003704.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFP1	ENST00000266263.10	TSL:1 MANE Select	c.196-93G>A		intron	N/A	ENSP00000266263.5
	ENSG00000249590	ENST00000439838.5	TSL:2	c.712-93G>A		intron	N/A	ENSP00000415178.1
	MTFP1	ENST00000614920.1	TSL:2	n.534G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42926 AN: 151956 Hom.: 6192 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.277 AC: 67687 AN: 244282 AF XY: 0.277

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.278

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.260 AC: 338072 AN: 1298710 Hom.: 45160 Cov.: 21 AF XY: 0.262 AC XY: 171668 AN XY: 654392

African (AFR) AF: 0.314 AC: 9468 AN: 30170

American (AMR) AF: 0.317 AC: 14039 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5203 AN: 25098

East Asian (EAS) AF: 0.270 AC: 10496 AN: 38834

South Asian (SAS) AF: 0.322 AC: 26474 AN: 82148

European-Finnish (FIN) AF: 0.291 AC: 15188 AN: 52174

Middle Eastern (MID) AF: 0.327 AC: 1608 AN: 4916

European-Non Finnish (NFE) AF: 0.249 AC: 240966 AN: 966210

Other (OTH) AF: 0.267 AC: 14630 AN: 54890

GnomAD4 genome AF: 0.282 AC: 42956 AN: 152074 Hom.: 6195 Cov.: 32 AF XY: 0.285 AC XY: 21154 AN XY: 74354

African (AFR) AF: 0.318 AC: 13203 AN: 41478

American (AMR) AF: 0.290 AC: 4435 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3468

East Asian (EAS) AF: 0.266 AC: 1380 AN: 5182

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4818

European-Finnish (FIN) AF: 0.287 AC: 3042 AN: 10588

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17645 AN: 67950

Other (OTH) AF: 0.273 AC: 575 AN: 2104

Alfa AF: 0.263 Hom.: 6988

Bravo AF: 0.282

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.2
DANN	Benign	0.85
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2072159; hg19: chr22-30823065; COSMIC: COSV56741897; COSMIC: COSV56741897;