17-4937837-C-T

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2753197.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 93 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A11NM_003562.5 linkc.849G>A p.Thr283Thr synonymous_variant Exon 8 of 8 ENST00000225665.12 NP_003553.2 Q02978-1Q6IBH0
SLC25A11NM_001165417.2 linkc.816G>A p.Thr272Thr synonymous_variant Exon 8 of 8 NP_001158889.1 Q6IBH0
SLC25A11NM_001165418.2 linkc.696G>A p.Thr232Thr synonymous_variant Exon 7 of 7 NP_001158890.1 Q6IBH0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A11ENST00000225665.12 linkc.849G>A p.Thr283Thr synonymous_variant Exon 8 of 8 1 NM_003562.5 ENSP00000225665.7 Q02978-1
SLC25A11ENST00000576951.1 linkc.816G>A p.Thr272Thr synonymous_variant Exon 8 of 8 5 ENSP00000458993.1 I3L1P8
SLC25A11ENST00000544061.6 linkc.696G>A p.Thr232Thr synonymous_variant Exon 7 of 7 3 ENSP00000440804.2 Q02978-2
SLC25A11ENST00000574710.1 linkn.1656G>A non_coding_transcript_exon_variant Exon 6 of 6 2

Frequencies

GnomAD3 genomes
AF:
0.000611
AC:
93
AN:
152198
Hom.:
0
Cov.:
33
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
GnomAD3 exomes
AF:
0.000617
AC:
155
AN:
251018
Hom.:
0
AF XY:
0.000516
AC XY:
70
AN XY:
135670
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 SAS exome
AF:
0.0000327
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.:
2
Cov.:
32
AF XY:
0.00105
AC XY:
761
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000760
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.00132
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.000611
AC:
93
AN:
152316
Hom.:
0
Cov.:
33
AF XY:
0.000577
AC XY:
43
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.000849
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00107
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000717
Hom.:
0
Bravo
AF:
0.000748
EpiCase
AF:
0.000818
EpiControl
AF:
0.00107

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 02, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
5.4
DANN
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs145172608; hg19: chr17-4841132; COSMIC: COSV52590996; COSMIC: COSV52590996; API