rs760504060

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-68483580-C-T
• chr10-68483580-C-A
• chr10-68483580-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_152707.4(SLC25A16):​c.851G>A​(p.Arg284Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000045 in 1,598,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: SLC25A16 NM_152707.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 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=0.1908193).

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>A	p.Arg284Gln	missense	Exon 9 of 9	NP_689920.1	P16260
	SLC25A16	NM_001324314.2		c.557G>A	p.Arg186Gln	missense	Exon 10 of 10	NP_001311243.1	B4DPV4
	SLC25A16	NM_001324315.1		c.557G>A	p.Arg186Gln	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>A	p.Arg284Gln	missense	Exon 9 of 9	ENSP00000476815.1	P16260
	SLC25A16	ENST00000493963.5	TSL:1	n.*779G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000476283.1	V9GY06
	SLC25A16	ENST00000493963.5	TSL:1	n.*779G>A		3_prime_UTR	Exon 10 of 10	ENSP00000476283.1	V9GY06

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000332 AC: 8 AN: 240894 AF XY: 0.0000307

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000484 AC: 70 AN: 1446172 Hom.: 0 Cov.: 28 AF XY: 0.0000501 AC XY: 36 AN XY: 718670

African (AFR) AF: 0.0000911 AC: 3 AN: 32940

American (AMR) AF: 0.0000240 AC: 1 AN: 41636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25640

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.000158 AC: 13 AN: 82446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000470 AC: 52 AN: 1105784

Other (OTH) AF: 0.0000167 AC: 1 AN: 59830

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.9
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.30	T
Polyphen		0.82	P
Vest4		0.054
MutPred		0.50		Loss of methylation at R284 (P = 0.0249)
MVP		0.57
MPC		0.34
ClinPred		0.17	T
GERP RS		3.6
Varity_R		0.067
gMVP		0.48
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;