10-68483541-C-A

Variant names:

• chr10-68483541-C-A
• NM_152707.4:c.890G>T

Variant summary

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

The NM_152707.4(SLC25A16):​c.890G>T​(p.Arg297Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A16 NM_152707.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10

Genes affected

SLC25A16 (HGNC:10986): (solute carrier family 25 member 16) This gene encodes a protein that contains three tandemly repeated mitochondrial carrier protein domains. The encoded protein is localized in the inner membrane and facilitates the rapid transport and exchange of molecules between the cytosol and the mitochondrial matrix space. This gene has a possible role in Graves' disease. [provided by RefSeq, Jul 2008]

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
SLC25A16	NM_152707.4	c.890G>T	p.Arg297Leu	missense_variant	Exon 9 of 9	ENST00000609923.6	NP_689920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A16	ENST00000609923.6	c.890G>T	p.Arg297Leu	missense_variant	Exon 9 of 9	1	NM_152707.4	ENSP00000476815.1
SLC25A16	ENST00000493963.5	n.*818G>T		non_coding_transcript_exon_variant	Exon 10 of 10	1		ENSP00000476283.1
SLC25A16	ENST00000493963.5	n.*818G>T		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000476283.1
SLC25A16	ENST00000265870.7	n.1773G>T		non_coding_transcript_exon_variant	Exon 8 of 8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.890G>T (p.R297L) alteration is located in exon 9 (coding exon 9) of the SLC25A16 gene. This alteration results from a G to T substitution at nucleotide position 890, causing the arginine (R) at amino acid position 297 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.022
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.42	N
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.35	T
Polyphen		0.087	B
Vest4		0.55
MutPred		0.55		Loss of methylation at R297 (P = 0.0112);
MVP		0.43
MPC		0.24
ClinPred		0.79	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: 47

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: chr10-70243298; COSMIC: COSV56263722; COSMIC: COSV56263722;