10-68527284-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152707.4(SLC25A16):c.92G>C(p.Arg31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,395,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R31L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC25A16 NM_152707.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22876284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A16	NM_152707.4	c.92G>C	p.Arg31Pro	missense_variant	1/9	ENST00000609923.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A16	ENST00000609923.6	c.92G>C	p.Arg31Pro	missense_variant	1/9	1	NM_152707.4	P1
SLC25A16	ENST00000493963.5	c.92G>C	p.Arg31Pro	missense_variant, NMD_transcript_variant	1/10	1
SLC25A16	ENST00000491102.2	c.92G>C	p.Arg31Pro	missense_variant, NMD_transcript_variant	1/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000135 AC: 2 AN: 147956 Hom.: 0 AF XY: 0.0000253 AC XY: 2 AN XY: 79124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000880

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1395900 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 688700

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: 0.0000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	0.95	D;D
PrimateAI	Pathogenic	0.89	D
Sift4G	Uncertain	0.048	D
Polyphen		0.30	B
Vest4		0.36
MutPred		0.56		Loss of MoRF binding (P = 0.0057);
MVP		0.42
MPC		0.49
ClinPred		0.77	D
GERP RS		3.5
Varity_R		0.44
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs771745123; hg19: chr10-70287041;