Genetic Variant SLC25A16:p.Gly187Glu (chr10-68493182-C-T) – ACMG Classification: Likely_pathogenic (7 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong

The NM_152707.4(SLC25A16):c.560G>A(p.Gly187Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC25A16
NM_152707.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

Publications

0 publications found

Variant links:

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]

SLC25A16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 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).

PP3

MetaRNN computational evidence supports a deleterious effect, 0.977

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A16	NM_152707.4	MANE Select	c.560G>A	p.Gly187Glu	missense	Exon 6 of 9	NP_689920.1	P16260
SLC25A16	NM_001324312.2		c.560G>A	p.Gly187Glu	missense	Exon 6 of 9	NP_001311241.1
SLC25A16	NM_001324313.2		c.560G>A	p.Gly187Glu	missense	Exon 6 of 8	NP_001311242.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A16	ENST00000609923.6	TSL:1 MANE Select	c.560G>A	p.Gly187Glu	missense	Exon 6 of 9	ENSP00000476815.1	P16260
SLC25A16	ENST00000493963.5	TSL:1	n.*488G>A		non_coding_transcript_exon	Exon 7 of 10	ENSP00000476283.1	V9GY06
SLC25A16	ENST00000493963.5	TSL:1	n.*488G>A		3_prime_UTR	Exon 7 of 10	ENSP00000476283.1	V9GY06

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000421

AC:

AN:

237612

AF XY:

0.00000777

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443472

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32462

American (AMR)

AF:

0.00

AC:

AN:

39698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25628

East Asian (EAS)

AF:

0.00

AC:

AN:

39430

South Asian (SAS)

AF:

0.00

AC:

AN:

82556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105006

Other (OTH)

AF:

0.00

AC:

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.62

MutationAssessor

Uncertain

2.8

PhyloP100

7.8

PrimateAI

Pathogenic

0.80

Sift4G

Benign

0.20

Polyphen

1.0

Vest4

0.98

MutPred

0.85

Loss of methylation at R190 (P = 0.0621)

MVP

0.81

MPC

0.77

ClinPred

0.95

GERP RS

6.1

Varity_R

0.48

gMVP

0.99

Mutation Taster

=18/82

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over