1-25829627-C-T

Variant names:

• chr1-25829627-C-T
• rs199554729
• ENST00000474295.5:c.461C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001099627.2(MTFR1L):​c.461C>T​(p.Pro154Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 1,614,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P154P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: MTFR1L NM_001099627.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.64

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.012030393).
• BP6: Variant 1-25829627-C-T is Benign according to our data. Variant chr1-25829627-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2569609.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFR1L	NM_001099625.2	c.570C>T	p.Thr190Thr	synonymous_variant	Exon 6 of 7	ENST00000374303.7	NP_001093095.1
MTFR1L	NM_001099627.2	c.461C>T	p.Pro154Leu	missense_variant	Exon 6 of 7		NP_001093097.1
MTFR1L	NM_001099626.2	c.570C>T	p.Thr190Thr	synonymous_variant	Exon 6 of 7		NP_001093096.1
MTFR1L	NM_019557.6	c.570C>T	p.Thr190Thr	synonymous_variant	Exon 6 of 7		NP_062457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFR1L	ENST00000374303.7	c.570C>T	p.Thr190Thr	synonymous_variant	Exon 6 of 7	1	NM_001099625.2	ENSP00000363421.2

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000276 AC: 69 AN: 249560 Hom.: 0 AF XY: 0.000266 AC XY: 36 AN XY: 135394

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000565

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000450 AC: 658 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.000443 AC XY: 322 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.000562

Gnomad4 OTH exome AF: 0.000232

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74472

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000854 Hom.: 39

Bravo AF: 0.000302

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000363 AC: 3

ExAC AF: 0.000166 AC: 20

EpiCase AF: 0.000491

EpiControl AF: 0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 26, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.2
DANN	Benign	0.69
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.44	.;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.012	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.10
Sift	Benign	0.094	T;T
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.0	B;B
Vest4		0.044
MVP		0.030
ClinPred		0.036	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs199554729; hg19: chr1-26156118;