chr1-25829728-C-G

Variant names:

• chr1-25829728-C-G
• rs781356037
• NM_001099625.2:c.671C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099625.2(MTFR1L):​c.671C>G​(p.Ser224Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S224L) has been classified 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: 1.89
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2521377).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099625.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFR1L	NM_001099625.2	MANE Select	c.671C>G	p.Ser224Trp	missense	Exon 6 of 7	NP_001093095.1	Q9H019-1
	MTFR1L	NM_001099626.2		c.671C>G	p.Ser224Trp	missense	Exon 6 of 7	NP_001093096.1	Q9H019-1
	MTFR1L	NM_019557.6		c.671C>G	p.Ser224Trp	missense	Exon 6 of 7	NP_062457.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFR1L	ENST00000374303.7	TSL:1 MANE Select	c.671C>G	p.Ser224Trp	missense	Exon 6 of 7	ENSP00000363421.2	Q9H019-1
	MTFR1L	ENST00000374300.7	TSL:1	c.671C>G	p.Ser224Trp	missense	Exon 6 of 7	ENSP00000363418.3	Q9H019-1
	MTFR1L	ENST00000374301.7	TSL:1	c.671C>G	p.Ser224Trp	missense	Exon 6 of 7	ENSP00000363419.3	Q9H019-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461614 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.91	T
PhyloP100		1.9
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.051
Sift	Benign	0.32	T
Sift4G	Benign	0.53	T
Polyphen		0.044	B
Vest4		0.24
MutPred		0.49		Loss of MoRF binding (P = 0.0112)
MVP		0.28
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.12
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs781356037; hg19: chr1-26156219;