10-68506590-T-A

Variant names:

• chr10-68506590-T-A
• rs764758123
• NM_152707.4:c.352A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152707.4(SLC25A16):​c.352A>T​(p.Lys118*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC25A16 NM_152707.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.68
• 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

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.352A>T	p.Lys118*	stop_gained	Exon 3 of 9	NP_689920.1	P16260
	SLC25A16	NM_001324312.2		c.352A>T	p.Lys118*	stop_gained	Exon 3 of 9	NP_001311241.1
	SLC25A16	NM_001324313.2		c.352A>T	p.Lys118*	stop_gained	Exon 3 of 8	NP_001311242.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A16	ENST00000609923.6	TSL:1 MANE Select	c.352A>T	p.Lys118*	stop_gained	Exon 3 of 9	ENSP00000476815.1	P16260
	SLC25A16	ENST00000493963.5	TSL:1	n.*280A>T		non_coding_transcript_exon	Exon 4 of 10	ENSP00000476283.1	V9GY06
	SLC25A16	ENST00000493963.5	TSL:1	n.*280A>T		3_prime_UTR	Exon 4 of 10	ENSP00000476283.1	V9GY06

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426104 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 709144

African (AFR) AF: 0.00 AC: 0 AN: 31638

American (AMR) AF: 0.00 AC: 0 AN: 37916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25098

East Asian (EAS) AF: 0.00 AC: 0 AN: 37698

South Asian (SAS) AF: 0.00 AC: 0 AN: 79178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097556

Other (OTH) AF: 0.00 AC: 0 AN: 58786

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		7.7
Vest4		0.45
GERP RS		5.8
Mutation Taster		=16/184	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs764758123; hg19: chr10-70266347;