chr1-25826623-C-T

Variant names:

• chr1-25826623-C-T
• rs201393961
• NM_001099625.2:c.248C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099625.2(MTFR1L):​c.248C>T​(p.Thr83Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000748 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (1 hom.)
• Consequence: MTFR1L NM_001099625.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16089961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFR1L	NM_001099625.2	c.248C>T	p.Thr83Met	missense_variant	Exon 5 of 7	ENST00000374303.7	NP_001093095.1
MTFR1L	NM_001099626.2	c.248C>T	p.Thr83Met	missense_variant	Exon 5 of 7		NP_001093096.1
MTFR1L	NM_019557.6	c.248C>T	p.Thr83Met	missense_variant	Exon 5 of 7		NP_062457.3
MTFR1L	NM_001099627.2	c.248C>T	p.Thr83Met	missense_variant	Exon 5 of 7		NP_001093097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFR1L	ENST00000374303.7	c.248C>T	p.Thr83Met	missense_variant	Exon 5 of 7	1	NM_001099625.2	ENSP00000363421.2

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000517 AC: 129 AN: 249472 Hom.: 0 AF XY: 0.000532 AC XY: 72 AN XY: 135360

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000918

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000781 AC: 1142 AN: 1461870 Hom.: 1 Cov.: 32 AF XY: 0.000792 AC XY: 576 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000754

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000941

Gnomad4 OTH exome AF: 0.000414

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37 AN XY: 74450

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000717 Hom.: 0

Bravo AF: 0.000348

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000246 AC: 1

ESP6500EA AF: 0.000838 AC: 7

ExAC AF: 0.000480 AC: 58

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.248C>T (p.T83M) alteration is located in exon 5 (coding exon 4) of the MTFR1L gene. This alteration results from a C to T substitution at nucleotide position 248, causing the threonine (T) at amino acid position 83 to be replaced by a methionine (M). 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	Benign	0.16
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0052	.;T;T;.;.;.;T;T;T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D;.;D;D;D;.;D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.5	.;L;.;L;.;L;.;L;.;L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.030	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.033	D;D;T;T;T;D;D;D;T;D;T
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T
Polyphen		1.0, 1.0	.;D;.;D;.;D;.;D;.;D;D
Vest4		0.64, 0.67, 0.67, 0.67, 0.64
MVP		0.39
MPC		1.0
ClinPred		0.054	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201393961; hg19: chr1-26153114; COSMIC: COSV65355493; COSMIC: COSV65355493;