1-25826381-C-A

Variant names:

• chr1-25826381-C-A
• rs752491963
• NM_001099625.2:c.209C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099625.2(MTFR1L):​c.209C>A​(p.Ala70Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTFR1L NM_001099625.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16
• Publications: 0 publications found

Genes affected

MTFR1L (HGNC:28836): (mitochondrial fission regulator 1 like) Predicted to be involved in aerobic respiration and mitochondrial fission. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3380501).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099625.2. 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
	MTFR1L	NM_001099625.2	MANE Select	c.209C>A	p.Ala70Glu	missense	Exon 4 of 7	NP_001093095.1	Q9H019-1
	MTFR1L	NM_001099626.2		c.209C>A	p.Ala70Glu	missense	Exon 4 of 7	NP_001093096.1	Q9H019-1
	MTFR1L	NM_019557.6		c.209C>A	p.Ala70Glu	missense	Exon 4 of 7	NP_062457.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFR1L	ENST00000374303.7	TSL:1 MANE Select	c.209C>A	p.Ala70Glu	missense	Exon 4 of 7	ENSP00000363421.2	Q9H019-1
	MTFR1L	ENST00000374300.7	TSL:1	c.209C>A	p.Ala70Glu	missense	Exon 4 of 7	ENSP00000363418.3	Q9H019-1
	MTFR1L	ENST00000374301.7	TSL:1	c.209C>A	p.Ala70Glu	missense	Exon 4 of 7	ENSP00000363419.3	Q9H019-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.52	N
PhyloP100		5.2
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	0.92	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.81	P
Vest4		0.69
MutPred		0.37		Gain of disorder (P = 0.0468)
MVP		0.16
MPC		0.76
ClinPred		0.79	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.70
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs752491963; hg19: chr1-26152872;