Genetic Variant NM_001349336.2:c.66T>C (chr5-135842435-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001349336.2(SLC25A48):c.66T>C(p.Val22Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 1,611,370 control chromosomes in the GnomAD database, including 524,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.78 ( 46647 hom., cov: 32)

Exomes 𝑓: 0.81 ( 477508 hom. )

Consequence

SLC25A48
NM_001349336.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.66

Publications

18 publications found

Variant links:

Genes affected

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) 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]

SLC25A48 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-2.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A48	NM_001349336.2 link	c.66T>C	p.Val22Val	synonymous_variant	Exon 2 of 8	ENST00000681962.1	NP_001336265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A48	ENST00000681962.1 link	c.66T>C	p.Val22Val	synonymous_variant	Exon 2 of 8		NM_001349336.2	ENSP00000506858.1		Q6ZT89-1

Frequencies

GnomAD3 genomes

AF:

0.781

AC:

118755

AN:

152004

Hom.:

46611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.823

Gnomad EAS

AF:

0.706

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.791

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.817

Gnomad OTH

AF:

0.805

GnomAD2 exomes

AF:

0.764

AC:

190457

AN:

249416

AF XY:

0.774

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.819

Gnomad EAS exome

AF:

0.702

Gnomad FIN exome

AF:

0.792

Gnomad NFE exome

AF:

0.820

Gnomad OTH exome

AF:

0.789

GnomAD4 exome

AF:

0.807

AC:

1177191

AN:

1459248

Hom.:

477508

Cov.:

AF XY:

0.808

AC XY:

586557

AN XY:

726018

show subpopulations

African (AFR)

AF:

0.739

AC:

24698

AN:

33412

American (AMR)

AF:

0.577

AC:

25764

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.816

AC:

21307

AN:

26114

East Asian (EAS)

AF:

0.685

AC:

27198

AN:

39692

South Asian (SAS)

AF:

0.785

AC:

67668

AN:

86178

European-Finnish (FIN)

AF:

0.796

AC:

42518

AN:

53392

Middle Eastern (MID)

AF:

0.880

AC:

5058

AN:

5746

European-Non Finnish (NFE)

AF:

0.824

AC:

914226

AN:

1109760

Other (OTH)

AF:

0.809

AC:

48754

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

11042

22083

33125

44166

55208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20856

41712

62568

83424

104280

<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:

0.781

AC:

118841

AN:

152122

Hom.:

46647

Cov.:

AF XY:

0.779

AC XY:

57944

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.746

AC:

30971

AN:

41494

American (AMR)

AF:

0.716

AC:

10954

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.823

AC:

2855

AN:

3470

East Asian (EAS)

AF:

0.705

AC:

3644

AN:

5168

South Asian (SAS)

AF:

0.783

AC:

3773

AN:

4820

European-Finnish (FIN)

AF:

0.791

AC:

8362

AN:

10578

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.817

AC:

55506

AN:

67974

Other (OTH)

AF:

0.805

AC:

1701

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1339

2679

4018

5358

6697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.806

Hom.:

232077

Bravo

AF:

0.770

Asia WGS

AF:

0.758

AC:

2638

AN:

3478

EpiCase

AF:

0.834

EpiControl

AF:

0.829

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

(source)

DANN

Benign

0.67

PhyloP100

-2.7

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over