17-75273287-C-A

Variant names:

• chr17-75273287-C-A
• rs371154305
• NM_001126121.2:c.*164G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001126121.2(SLC25A19):​c.*164G>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 0.00000189 in 530,410 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: 0.0000019 (0 hom.)
• Consequence: SLC25A19 NM_001126121.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 0 publications found

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]

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A19	NM_001126121.2	MANE Select	c.*164G>T		3_prime_UTR	Exon 8 of 8	NP_001119593.1	Q9HC21-1
	SLC25A19	NM_001126122.2		c.*164G>T		3_prime_UTR	Exon 7 of 7	NP_001119594.1	Q9HC21-1
	SLC25A19	NM_021734.5		c.*164G>T		3_prime_UTR	Exon 8 of 8	NP_068380.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A19	ENST00000416858.7	TSL:1 MANE Select	c.*164G>T		3_prime_UTR	Exon 8 of 8	ENSP00000397818.2	Q9HC21-1
	SLC25A19	ENST00000402418.7	TSL:1	c.*164G>T		3_prime_UTR	Exon 6 of 6	ENSP00000385312.3	Q9HC21-1
	SLC25A19	ENST00000582822.1	TSL:3	c.152G>T	p.Gly51Val	missense splice_region	Exon 3 of 3	ENSP00000462401.1	J3KSB1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000189 AC: 1 AN: 530410 Hom.: 0 Cov.: 6 AF XY: 0.00000355 AC XY: 1 AN XY: 282084

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14810

American (AMR) AF: 0.00 AC: 0 AN: 26556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15892

East Asian (EAS) AF: 0.00 AC: 0 AN: 31774

South Asian (SAS) AF: 0.00 AC: 0 AN: 52000

European-Finnish (FIN) AF: 0.0000329 AC: 1 AN: 30366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 327556

Other (OTH) AF: 0.00 AC: 0 AN: 29176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		0.34

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

Other links and lift over

dbSNP: rs371154305; hg19: chr17-73269368;