chr19-6442006-A-G

Position:

• chr19-6442006-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024103.3(SLC25A23):​c.1376T>C​(p.Met459Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SLC25A23 NM_024103.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65

Genes affected

SLC25A23 (HGNC:19375): (solute carrier family 25 member 23) Predicted to enable ATP transmembrane transporter activity. Involved in calcium import into the mitochondrion; positive regulation of mitochondrial calcium ion concentration; and regulation of cellular hyperosmotic salinity response. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A23 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28698823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A23	NM_024103.3	c.1376T>C	p.Met459Thr	missense_variant	10/10	ENST00000301454.9	NP_077008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A23	ENST00000301454.9	c.1376T>C	p.Met459Thr	missense_variant	10/10	1	NM_024103.3	ENSP00000301454.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461724 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727164

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.1376T>C (p.M459T) alteration is located in exon 10 (coding exon 10) of the SLC25A23 gene. This alteration results from a T to C substitution at nucleotide position 1376, causing the methionine (M) at amino acid position 459 to be replaced by a threonine (T). 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	Benign	0.19
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Benign	0.89
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.25	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.25
Sift	Benign	0.44	T
Sift4G	Benign	0.35	T
Polyphen		0.0090	B
Vest4		0.16
MutPred		0.81		Gain of methylation at K460 (P = 0.0253);
MVP		0.63
MPC		0.39
ClinPred		0.35	T
GERP RS		5.0
Varity_R		0.19
gMVP		0.78

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: chr19-6442017;