chr17-75273496-G-A

Variant names:

• chr17-75273496-G-A
• rs113513403
• NM_001126121.2:c.918C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM2 BP4_Moderate BP6_Very_Strong

The NM_021734.5(SLC25A19):​c.918C>T​(p.Phe306Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000547 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SLC25A19 NM_021734.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.45
• 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: Benign. The variant received -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 17-75273496-G-A is Benign according to our data. Variant chr17-75273496-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 436747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021734.5. 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.918C>T	p.Phe306Phe	synonymous	Exon 8 of 8	NP_001119593.1
	SLC25A19	NM_001126122.2		c.918C>T	p.Phe306Phe	synonymous	Exon 7 of 7	NP_001119594.1
	SLC25A19	NM_021734.5		c.918C>T	p.Phe306Phe	synonymous	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.918C>T	p.Phe306Phe	synonymous	Exon 8 of 8	ENSP00000397818.2
	SLC25A19	ENST00000402418.7	TSL:1	c.918C>T	p.Phe306Phe	synonymous	Exon 6 of 6	ENSP00000385312.3
	SLC25A19	ENST00000320362.7	TSL:2	c.918C>T	p.Phe306Phe	synonymous	Exon 9 of 9	ENSP00000319574.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461808 Hom.: 0 Cov.: 64 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111990

Other (OTH) AF: 0.0000331 AC: 2 AN: 60390

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.84
PhyloP100		5.5
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs113513403; hg19: chr17-73269577;