Genetic Variant SLC25A11:p.Thr283Thr (chr17-4937837-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003562.5(SLC25A11):c.849G>A(p.Thr283Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,114 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

SLC25A11
NM_003562.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.95

Publications

0 publications found

Variant links:

Genes affected

SLC25A11 (HGNC:10981): (solute carrier family 25 member 11) The oxoglutarate/malate carrier transports 2-oxoglutarate across the inner membranes of mitochondria in an electroneutral exchange for malate or other dicarboxylic acids (summary by Iacobazzi et al., 1992 [PubMed 1457818]).[supplied by OMIM, Jan 2011]

SLC25A11 Gene-Disease associations (from GenCC):

hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pheochromocytoma/paraganglioma syndrome 6
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

SLC25A11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-4937837-C-T is Benign according to our data. Variant chr17-4937837-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2753197.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 93 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003562.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A11	NM_003562.5	MANE Select	c.849G>A	p.Thr283Thr	synonymous	Exon 8 of 8	NP_003553.2
SLC25A11	NM_001165417.2		c.816G>A	p.Thr272Thr	synonymous	Exon 8 of 8	NP_001158889.1
SLC25A11	NM_001165418.2		c.696G>A	p.Thr232Thr	synonymous	Exon 7 of 7	NP_001158890.1	Q02978-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A11	ENST00000225665.12	TSL:1 MANE Select	c.849G>A	p.Thr283Thr	synonymous	Exon 8 of 8	ENSP00000225665.7	Q02978-1
SLC25A11	ENST00000940187.1		c.933G>A	p.Thr311Thr	synonymous	Exon 7 of 7	ENSP00000610246.1
SLC25A11	ENST00000576951.1	TSL:5	c.816G>A	p.Thr272Thr	synonymous	Exon 8 of 8	ENSP00000458993.1	I3L1P8

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000617

AC:

155

AN:

251018

AF XY:

0.000516

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00106

AC:

1554

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

761

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33478

American (AMR)

AF:

0.000760

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00132

AC:

1466

AN:

1111982

Other (OTH)

AF:

0.000646

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

179

268

358

447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000611

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41560

American (AMR)

AF:

0.000849

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000717

Hom.:

Bravo

AF:

0.000748

EpiCase

AF:

0.000818

EpiControl

AF:

0.00107

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.4

(source)

DANN

Benign

0.87

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over