Variant rs34400381 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_182556.4(SLC25A45):c.853C>T(p.Arg285Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,613,676 control chromosomes in the GnomAD database, including 911 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 61 hom., cov: 33)

Exomes 𝑓: 0.031 ( 850 hom. )

Consequence

SLC25A45
NM_182556.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

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]

SLC25A45 links:

FRMD8 (HGNC:):

FRMD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027039945).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.024 (3664/152380) while in subpopulation NFE AF= 0.0347 (2364/68038). AF 95% confidence interval is 0.0336. There are 61 homozygotes in gnomad4. There are 1861 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A45	NM_182556.4 linkuse as main transcript	c.853C>T	p.Arg285Cys	missense_variant	7/7	ENST00000398802.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A45	ENST00000398802.6 linkuse as main transcript	c.853C>T	p.Arg285Cys	missense_variant	7/7	5	NM_182556.4	P1	Q8N413-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3666

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00593

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.0618

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0260

AC:

6475

AN:

248858

Hom.:

128

AF XY:

0.0267

AC XY:

3612

AN XY:

135032

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.0139

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00382

Gnomad FIN exome

AF:

0.0669

Gnomad NFE exome

AF:

0.0347

Gnomad OTH exome

AF:

0.0383

GnomAD4 exome

AF:

0.0308

AC:

45016

AN:

1461296

Hom.:

850

Cov.:

AF XY:

0.0303

AC XY:

22038

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.00556

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00395

Gnomad4 FIN exome

AF:

0.0652

Gnomad4 NFE exome

AF:

0.0341

Gnomad4 OTH exome

AF:

0.0287

GnomAD4 genome

AF:

0.0240

AC:

3664

AN:

152380

Hom.:

Cov.:

AF XY:

0.0250

AC XY:

1861

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00591

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0618

Gnomad4 NFE

AF:

0.0347

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0295

Hom.:

109

Bravo

AF:

0.0209

TwinsUK

AF:

0.0286

AC:

106

ALSPAC

AF:

0.0361

AC:

139

ESP6500AA

AF:

0.00739

AC:

ESP6500EA

AF:

0.0342

AC:

286

ExAC

AF:

0.0262

AC:

3166

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0321

EpiControl

AF:

0.0313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.;T;.;.

Eigen

Benign

0.12

Eigen_PC

Benign

-0.092

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.87

.;D;D;D;D

MetaRNN

Benign

0.0027

T;T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.9

M;.;M;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.8

D;D;D;D;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D

Polyphen

0.99

D;D;D;.;D

Vest4

0.024

MPC

0.65

ClinPred

0.038

GERP RS

3.8

Varity_R

0.31

gMVP

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over