rs1321899820

Variant names:

• chr5-121852030-C-A
• rs1321899820
• NM_177478.2:c.67C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-121852030-C-A
• chr5-121852030-C-G
• chr5-121852030-C-T

Variant summary

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

The NM_177478.2(FTMT):​c.67C>A​(p.Arg23Ser) 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. 14/24 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. R23C) 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: -0.298
• Publications: 7 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.67C>A	p.Arg23Ser	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.67C>A	p.Arg23Ser	missense	Exon 1 of 1	ENSP00000313691.1	Q8N4E7
	ENSG00000303256	ENST00000793240.1		n.-181G>T		upstream_gene	N/A
	ENSG00000303256	ENST00000793241.1		n.-212G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.32
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.30
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.061
Sift	Benign	0.25	T
Sift4G	Benign	0.59	T
Polyphen		0.010	B
Vest4		0.17
MutPred		0.32		Loss of helix (P = 0.0167)
MVP		0.41
MPC		0.47
ClinPred		0.053	T
GERP RS		0.071
PromoterAI		0.057	Neutral
Varity_R		0.081
gMVP		0.56
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1321899820; hg19: chr5-121187725; COSMIC: COSV100360292;