11-65376970-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182556.4(SLC25A45):​c.446A>G​(p.His149Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000924 in 1,613,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000092 ( 1 hom. )

Consequence

SLC25A45
NM_182556.4 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55
Variant links:
Genes affected
SLC25A45 (HGNC:27442): (solute carrier family 25 member 45) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
FRMD8 (HGNC:25462): (FERM domain containing 8) Involved in positive regulation of tumor necrosis factor production. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19598383).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC25A45NM_182556.4 linkc.446A>G p.His149Arg missense_variant Exon 6 of 7 ENST00000398802.6 NP_872362.4 Q8N413-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A45ENST00000398802.6 linkc.446A>G p.His149Arg missense_variant Exon 6 of 7 5 NM_182556.4 ENSP00000381782.1 Q8N413-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000198
AC:
49
AN:
247280
Hom.:
1
AF XY:
0.000179
AC XY:
24
AN XY:
134292
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00454
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000268
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.0000924
AC:
135
AN:
1460970
Hom.:
1
Cov.:
33
AF XY:
0.0000936
AC XY:
68
AN XY:
726784
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00388
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152176
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000329
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.000141
AC:
17
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.446A>G (p.H149R) alteration is located in exon 6 (coding exon 5) of the SLC25A45 gene. This alteration results from a A to G substitution at nucleotide position 446, causing the histidine (H) at amino acid position 149 to be replaced by an arginine (R). 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
Benign
0.30
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.;T;.;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.91
.;D;D;D;D
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.20
T;T;T;T;T
MetaSVM
Uncertain
0.12
D
MutationAssessor
Benign
1.7
L;.;L;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-6.5
D;D;D;D;D
REVEL
Pathogenic
0.68
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.010
D;D;D;D;D
Polyphen
1.0
D;D;D;.;D
Vest4
0.66
MVP
0.61
MPC
0.70
ClinPred
0.33
T
GERP RS
5.1
Varity_R
0.86
gMVP
0.76

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: rs199936582; hg19: chr11-65144441; API