14-24131745-C-T

Variant names:

• chr14-24131745-C-T
• NM_203402.3:c.182C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203402.3(FITM1):​c.182C>T​(p.Ala61Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FITM1 NM_203402.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04

Genes affected

FITM1 (HGNC:33714): (fat storage inducing transmembrane protein 1) Predicted to enable diacylglycerol binding activity and triglyceride binding activity. Predicted to be involved in lipid droplet formation; phospholipid biosynthetic process; and positive regulation of sequestering of triglyceride. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259371 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FITM1	NM_203402.3	c.182C>T	p.Ala61Val	missense_variant	Exon 1 of 2	ENST00000267426.6	NP_981947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FITM1	ENST00000267426.6	c.182C>T	p.Ala61Val	missense_variant	Exon 1 of 2	1	NM_203402.3	ENSP00000267426.5
ENSG00000259371	ENST00000558325.2	c.764C>T	p.Ala255Val	missense_variant	Exon 4 of 4	5		ENSP00000453089.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461690 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.182C>T (p.A61V) alteration is located in exon 1 (coding exon 1) of the FITM1 gene. This alteration results from a C to T substitution at nucleotide position 182, causing the alanine (A) at amino acid position 61 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0042	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.34	N
REVEL	Uncertain	0.43
Sift	Benign	0.16	T
Sift4G	Uncertain	0.027	D
Polyphen		0.97	D
Vest4		0.69
MutPred		0.39		Gain of catalytic residue at A58 (P = 0);
MVP		0.65
MPC		0.49
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24600954;