rs199554729

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-25829627-C-A
• chr1-25829627-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099627.2(MTFR1L):​c.461C>A​(p.Pro154Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P154L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTFR1L NM_001099627.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031805545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099627.2. 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.570C>A	p.Thr190Thr	synonymous	Exon 6 of 7	NP_001093095.1	Q9H019-1
	MTFR1L	NM_001099627.2		c.461C>A	p.Pro154Gln	missense	Exon 6 of 7	NP_001093097.1	Q9H019-2
	MTFR1L	NM_001099626.2		c.570C>A	p.Thr190Thr	synonymous	Exon 6 of 7	NP_001093096.1	Q9H019-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFR1L	ENST00000474295.5	TSL:1	c.461C>A	p.Pro154Gln	missense	Exon 6 of 7	ENSP00000435461.1	Q9H019-2
	MTFR1L	ENST00000374303.7	TSL:1 MANE Select	c.570C>A	p.Thr190Thr	synonymous	Exon 6 of 7	ENSP00000363421.2	Q9H019-1
	MTFR1L	ENST00000374300.7	TSL:1	c.570C>A	p.Thr190Thr	synonymous	Exon 6 of 7	ENSP00000363418.3	Q9H019-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.5
DANN	Benign	0.96
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.6
PROVEAN	Benign	0.47	N
REVEL	Benign	0.095
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.011	D
Polyphen		0.0	B
Vest4		0.084
MutPred		0.40		Gain of helix (P = 0.0082)
MVP		0.030
ClinPred		0.10	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=77/23	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: rs199554729; hg19: chr1-26156118;