1-25829595-T-C

Variant names:

• chr1-25829595-T-C
• rs2048210428
• NM_001099625.2:c.538T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099625.2(MTFR1L):​c.538T>C​(p.Ser180Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,888 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MTFR1L NM_001099625.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32252052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTFR1L	NM_001099625.2	c.538T>C	p.Ser180Pro	missense_variant	Exon 6 of 7	ENST00000374303.7	NP_001093095.1
MTFR1L	NM_001099626.2	c.538T>C	p.Ser180Pro	missense_variant	Exon 6 of 7		NP_001093096.1
MTFR1L	NM_019557.6	c.538T>C	p.Ser180Pro	missense_variant	Exon 6 of 7		NP_062457.3
MTFR1L	NM_001099627.2	c.452-23T>C		intron_variant	Intron 5 of 6		NP_001093097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFR1L	ENST00000374303.7	c.538T>C	p.Ser180Pro	missense_variant	Exon 6 of 7	1	NM_001099625.2	ENSP00000363421.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.538T>C (p.S180P) 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 538, causing the serine (S) at amino acid position 180 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	0.17
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0068	T;.;T;.;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.80	T;T;T;T;.;.
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;.;.;.;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	1.6	N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.076	T;D;D;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T
Polyphen		0.98	D;.;.;D;D;D
Vest4		0.33
MutPred		0.65		Gain of loop (P = 0.024);.;.;.;Gain of loop (P = 0.024);Gain of loop (P = 0.024);
MVP		0.27
MPC		1.2
ClinPred		0.71	D
GERP RS		6.2
Varity_R		0.16
gMVP		0.26

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: rs2048210428; hg19: chr1-26156086;