rs2072159

Positions:

• chr22-30427078-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTFP1	NM_016498.5	c.196-93G>A		intron_variant		ENST00000266263.10	NP_057582.2
MTFP1	NM_001003704.3	c.195+234G>A		intron_variant			NP_001003704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTFP1	ENST00000266263.10	c.196-93G>A		intron_variant		1	NM_016498.5	ENSP00000266263.5
ENSG00000249590	ENST00000439838.5	c.712-93G>A		intron_variant		2		ENSP00000415178.1

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

GnomAD3 exomes AF: 0.277 AC: 67687 AN: 244282 Hom.: 9458 AF XY: 0.277 AC XY: 36743 AN XY: 132864

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 SAS exome AF: 0.322

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

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.267

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

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.273

Alfa AF: 0.260 Hom.: 5317

Bravo AF: 0.282

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.2
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072159; hg19: chr22-30823065; COSMIC: COSV56741897; COSMIC: COSV56741897;