Genetic Variant SLC25A19:c.*113G>T (chr17-75273338-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001126121.2(SLC25A19):c.*113G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,110,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

SLC25A19
NM_001126121.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.422

Publications

0 publications found

Variant links:

Genes affected

SLC25A19 (HGNC:14409): (solute carrier family 25 member 19) This gene encodes a mitochondrial protein that is a member of the solute carrier family. Although this protein was initially thought to be the mitochondrial deoxynucleotide carrier involved in the uptake of deoxynucleotides into the matrix of the mitochondria, further studies have demonstrated that this protein instead functions as the mitochondrial thiamine pyrophosphate carrier, which transports thiamine pyrophosphates into mitochondria. Mutations in this gene cause microcephaly, Amish type, a metabolic disease that results in severe congenital microcephaly, severe 2-ketoglutaric aciduria, and death within the first year. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

SLC25A19 links:

MIF4GD-DT (HGNC:55335): (MIF4GD divergent transcript)

MIF4GD-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126121.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A19	NM_001126121.2	MANE Select	c.*113G>T	3_prime_UTR	Exon 8 of 8	NP_001119593.1	Q9HC21-1
SLC25A19	NM_001126122.2		c.*113G>T	3_prime_UTR	Exon 7 of 7	NP_001119594.1	Q9HC21-1
SLC25A19	NM_021734.5		c.*113G>T	3_prime_UTR	Exon 8 of 8	NP_068380.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A19	ENST00000416858.7	TSL:1 MANE Select	c.*113G>T	3_prime_UTR	Exon 8 of 8	ENSP00000397818.2	Q9HC21-1
SLC25A19	ENST00000402418.7	TSL:1	c.*113G>T	3_prime_UTR	Exon 6 of 6	ENSP00000385312.3	Q9HC21-1
SLC25A19	ENST00000320362.7	TSL:2	c.*113G>T	3_prime_UTR	Exon 9 of 9	ENSP00000319574.3	Q9HC21-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000750

AC:

AN:

133418

AF XY:

0.0000138

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000631

AC:

AN:

1110222

Hom.:

Cov.:

AF XY:

0.00000894

AC XY:

AN XY:

559050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26448

American (AMR)

AF:

0.00

AC:

AN:

34760

Ashkenazi Jewish (ASJ)

AF:

0.0000435

AC:

AN:

22982

East Asian (EAS)

AF:

0.000146

AC:

AN:

34364

South Asian (SAS)

AF:

0.0000137

AC:

AN:

72888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3568

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

832254

Other (OTH)

AF:

0.00

AC:

AN:

48760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.67

(source)

DANN

Benign

0.66

PhyloP100

-0.42

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over