Variant 10-68516765-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152707.4(SLC25A16):c.209A>T(p.His70Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000482 in 1,453,032 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: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC25A16
NM_152707.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.49

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40790993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A16	NM_152707.4 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant	2/9	ENST00000609923.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC25A16	ENST00000609923.6 linkuse as main transcript	c.209A>T	p.His70Leu	missense_variant	2/9	1	NM_152707.4	P1
SLC25A16	ENST00000493963.5 linkuse as main transcript	c.*137A>T		3_prime_UTR_variant, NMD_transcript_variant	3/10	1
SLC25A16	ENST00000265870.7 linkuse as main transcript	n.1214A>T		non_coding_transcript_exon_variant	2/8	2
SLC25A16	ENST00000491102.2 linkuse as main transcript	c.*112A>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249958

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135120

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1453032

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723204

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.209A>T (p.H70L) alteration is located in exon 2 (coding exon 2) of the SLC25A16 gene. This alteration results from a A to T substitution at nucleotide position 209, causing the histidine (H) at amino acid position 70 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.40

Eigen

Benign

0.019

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.012

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

Sift4G

Uncertain

0.022

Polyphen

0.017

Vest4

0.66

MutPred

0.41

Loss of disorder (P = 0.1053);

MVP

0.37

MPC

0.63

ClinPred

0.89

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.67

gMVP

0.77

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over