rs770755210

Variant names:

• chr1-25829689-C-A
• rs770755210
• NM_001099625.2:c.632C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-25829689-C-A
• chr1-25829689-C-T

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.632C>A​(p.Pro211His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P211L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MTFR1L NM_001099625.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• 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=0.14460805).

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.632C>A	p.Pro211His	missense	Exon 6 of 7	NP_001093095.1	Q9H019-1
	MTFR1L	NM_001099626.2		c.632C>A	p.Pro211His	missense	Exon 6 of 7	NP_001093096.1	Q9H019-1
	MTFR1L	NM_019557.6		c.632C>A	p.Pro211His	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.632C>A	p.Pro211His	missense	Exon 6 of 7	ENSP00000363421.2	Q9H019-1
	MTFR1L	ENST00000374300.7	TSL:1	c.632C>A	p.Pro211His	missense	Exon 6 of 7	ENSP00000363418.3	Q9H019-1
	MTFR1L	ENST00000374301.7	TSL:1	c.632C>A	p.Pro211His	missense	Exon 6 of 7	ENSP00000363419.3	Q9H019-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.92
Eigen	Benign	-0.097
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.3
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.073
Sift	Benign	0.034	D
Sift4G	Uncertain	0.059	T
Polyphen		0.69	P
Vest4		0.14
MutPred		0.45		Gain of MoRF binding (P = 0.0772)
MVP		0.18
ClinPred		0.44	T
GERP RS		5.0
Varity_R		0.097
Mutation Taster		=79/21	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: rs770755210; hg19: chr1-26156180;