Genetic Variant MTFR1L:p.Ser161Pro (chr1-25829538-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099625.2(MTFR1L):c.481T>C(p.Ser161Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MTFR1L
NM_001099625.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65

Variant links:

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]

MTFR1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1528554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFR1L	NM_001099625.2 link	c.481T>C	p.Ser161Pro	missense_variant	Exon 6 of 7	ENST00000374303.7	NP_001093095.1	Q9H019-1A0A0S2Z5H6
MTFR1L	NM_001099626.2 link	c.481T>C	p.Ser161Pro	missense_variant	Exon 6 of 7		NP_001093096.1	Q9H019-1A0A0S2Z5H6
MTFR1L	NM_019557.6 link	c.481T>C	p.Ser161Pro	missense_variant	Exon 6 of 7		NP_062457.3	Q9H019-1A0A0S2Z5H6
MTFR1L	NM_001099627.2 link	c.452-80T>C		intron_variant	Intron 5 of 6		NP_001093097.1	Q9H019-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFR1L	ENST00000374303.7 link	c.481T>C	p.Ser161Pro	missense_variant	Exon 6 of 7	1	NM_001099625.2	ENSP00000363421.2		Q9H019-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

249030

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461492

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000576

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.481T>C (p.S161P) alteration is located in exon 6 (coding exon 5) of the MTFR1L gene. This alteration results from a T to C substitution at nucleotide position 481, causing the serine (S) at amino acid position 161 to be replaced by a proline (P). 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

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;.;T;T;T;T

Eigen

Benign

0.0021

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;D;D;.;T;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.;L;.;L

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.37

N;D;D;N;N;N

REVEL

Benign

0.078

Sift

Benign

0.084

T;D;D;T;D;T

Sift4G

Benign

0.24

T;T;T;T;T;T

Polyphen

0.025

B;.;.;B;.;B

Vest4

0.49

MutPred

0.57

Gain of catalytic residue at S161 (P = 0.0118);.;.;Gain of catalytic residue at S161 (P = 0.0118);Gain of catalytic residue at S161 (P = 0.0118);Gain of catalytic residue at S161 (P = 0.0118);

MVP

0.22

MPC

1.2

ClinPred

0.20

GERP RS

5.1

Varity_R

0.15

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over