1-25826354-C-A

Variant names:

• chr1-25826354-C-A
• NM_001099625.2:c.182C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099625.2(MTFR1L):​c.182C>A​(p.Thr61Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.99

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFR1L	NM_001099625.2	c.182C>A	p.Thr61Asn	missense_variant	Exon 4 of 7	ENST00000374303.7	NP_001093095.1
MTFR1L	NM_001099626.2	c.182C>A	p.Thr61Asn	missense_variant	Exon 4 of 7		NP_001093096.1
MTFR1L	NM_019557.6	c.182C>A	p.Thr61Asn	missense_variant	Exon 4 of 7		NP_062457.3
MTFR1L	NM_001099627.2	c.182C>A	p.Thr61Asn	missense_variant	Exon 4 of 7		NP_001093097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFR1L	ENST00000374303.7	c.182C>A	p.Thr61Asn	missense_variant	Exon 4 of 7	1	NM_001099625.2	ENSP00000363421.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.182C>A (p.T61N) alteration is located in exon 4 (coding exon 3) of the MTFR1L gene. This alteration results from a C to A substitution at nucleotide position 182, causing the threonine (T) at amino acid position 61 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	0.0090	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;T;.;.;.;T;T;T;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;.;D;D;D;.;D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.9	.;L;.;L;.;L;.;L;.;L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0, 1.0	.;D;.;D;.;D;.;D;.;D;D
Vest4		0.90, 0.92, 0.92, 0.89, 0.91
MutPred		0.57		Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);Loss of phosphorylation at T61 (P = 0.019);
MVP		0.42
MPC		1.1
ClinPred		0.88	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-26152845;