Genetic Variant FTMT:p.Leu7Phe (chr5-121851982-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_177478.2(FTMT):c.19C>T(p.Leu7Phe) 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FTMT
NM_177478.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.599

Publications

0 publications found

Variant links:

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]

FTMT links:

LOC105379149 (HGNC:):

LOC105379149 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036623806).

BP6

Variant 5-121851982-C-T is Benign according to our data. Variant chr5-121851982-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3517667.Status of the report is criteria_provided_single_submitter, 1 stars.

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.19C>T	p.Leu7Phe	missense	Exon 1 of 1	NP_803431.1	Q8N4E7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FTMT	ENST00000321339.3	TSL:6 MANE Select	c.19C>T	p.Leu7Phe	missense	Exon 1 of 1	ENSP00000313691.1	Q8N4E7
ENSG00000303256	ENST00000793240.1		n.-133G>A		upstream_gene	N/A
ENSG00000303256	ENST00000793241.1		n.-164G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1438248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716120

African (AFR)

AF:

0.00

AC:

AN:

31172

American (AMR)

AF:

0.00

AC:

AN:

43678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25580

East Asian (EAS)

AF:

0.00

AC:

AN:

38102

South Asian (SAS)

AF:

0.00

AC:

AN:

85740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4098

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106664

Other (OTH)

AF:

0.00

AC:

AN:

59610

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.11

(source)

DANN

Benign

0.089

DEOGEN2

Benign

0.23

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.43

M_CAP

Benign

0.0098

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.52

PhyloP100

-0.60

PrimateAI

Benign

0.36

PROVEAN

Benign

0.19

REVEL

Benign

0.038

Sift

Benign

1.0

Sift4G

Benign

0.77

Polyphen

0.0

Vest4

0.10

MutPred

0.20

Gain of methylation at R6 (P = 0.1)

MVP

0.19

MPC

0.31

ClinPred

0.041

GERP RS

-0.76

PromoterAI

0.017

Neutral

(source)

Varity_R

0.035

gMVP

0.27

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over