chr5-121852613-A-G

Variant names:

• chr5-121852613-A-G
• rs1400613805
• NM_177478.2:c.650A>G

Variant summary

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

The NM_177478.2(FTMT):​c.650A>G​(p.Lys217Arg) 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. 17/22 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. K217M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FTMT NM_177478.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

FTMT (HGNC:17345): (ferritin mitochondrial) Predicted to enable ferric iron binding activity and ferrous iron binding activity. Involved in several processes, including cellular iron ion homeostasis; positive regulation of aconitate hydratase activity; and positive regulation of succinate dehydrogenase activity. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC105379149 (HGNC:):

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=0.09384537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177478.2. 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
	FTMT	NM_177478.2	MANE Select	c.650A>G	p.Lys217Arg	missense	Exon 1 of 1	NP_803431.1	Q8N4E7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTMT	ENST00000321339.3	TSL:6 MANE Select	c.650A>G	p.Lys217Arg	missense	Exon 1 of 1	ENSP00000313691.1	Q8N4E7

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	0.067
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.30
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.063
Sift	Benign	0.56	T
Sift4G	Benign	0.97	T
Polyphen		0.0020	B
Vest4		0.047
MutPred		0.44		Gain of methylation at K217 (P = 0.1062)
MVP		0.25
MPC		0.24
ClinPred		0.066	T
GERP RS		-0.30
Varity_R		0.12
gMVP		0.11
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1400613805; hg19: chr5-121188308;