chr1-108136697-C-A

Position:

• chr1-108136697-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013386.5(SLC25A24):​c.1390G>T​(p.Val464Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A24 NM_013386.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

SLC25A24 (HGNC:20662): (solute carrier family 25 member 24) This gene encodes a carrier protein that transports ATP-Mg exchanging it for phosphate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A24	NM_013386.5	c.1390G>T	p.Val464Phe	missense_variant	10/10	ENST00000565488.6
SLC25A24	NM_213651.3	c.1333G>T	p.Val445Phe	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A24	ENST00000565488.6	c.1390G>T	p.Val464Phe	missense_variant	10/10	1	NM_013386.5	P1
SLC25A24	ENST00000370041.4	c.1333G>T	p.Val445Phe	missense_variant	10/10	1
SLC25A24	ENST00000264128.13	c.*969G>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	5
SLC25A24	ENST00000648874.1	c.*711G>T		3_prime_UTR_variant, NMD_transcript_variant	11/11

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.1390G>T (p.V464F) alteration is located in exon 10 (coding exon 10) of the SLC25A24 gene. This alteration results from a G to T substitution at nucleotide position 1390, causing the valine (V) at amino acid position 464 to be replaced by a phenylalanine (F). 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	0.64
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.4	D;D
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.83
MutPred		0.70		Loss of sheet (P = 0.0817);.;
MVP		0.88
MPC		0.87
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.88
gMVP		0.87

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: chr1-108679319;