10-68483580-C-G

Variant names:

• chr10-68483580-C-G
• rs760504060
• NM_152707.4:c.851G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_152707.4(SLC25A16):​c.851G>C​(p.Arg284Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R284Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A16 NM_152707.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.57984 (below the threshold of 3.09). Trascript score misZ: -0.19574 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.27072337).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152707.4. 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
	SLC25A16	NM_152707.4	MANE Select	c.851G>C	p.Arg284Pro	missense	Exon 9 of 9	NP_689920.1	P16260
	SLC25A16	NM_001324314.2		c.557G>C	p.Arg186Pro	missense	Exon 10 of 10	NP_001311243.1	B4DPV4
	SLC25A16	NM_001324315.1		c.557G>C	p.Arg186Pro	missense	Exon 9 of 9	NP_001311244.1	B4DPV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A16	ENST00000609923.6	TSL:1 MANE Select	c.851G>C	p.Arg284Pro	missense	Exon 9 of 9	ENSP00000476815.1	P16260
	SLC25A16	ENST00000493963.5	TSL:1	n.*779G>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000476283.1	V9GY06
	SLC25A16	ENST00000493963.5	TSL:1	n.*779G>C		3_prime_UTR	Exon 10 of 10	ENSP00000476283.1	V9GY06

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.067
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.20	T
Polyphen		0.087	B
Vest4		0.35
MutPred		0.59		Loss of methylation at R284 (P = 0.0249)
MVP		0.53
MPC		0.53
ClinPred		0.91	D
GERP RS		3.6
Varity_R		0.44
gMVP		0.83
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs760504060; hg19: chr10-70243337;