rs797045968

Variant names:

• chr17-75273625-C-A
• rs797045968
• NM_001126121.2:c.789G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-75273625-C-A
• chr17-75273625-C-G
• chr17-75273625-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001126121.2(SLC25A19):​c.789G>T​(p.Lys263Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC25A19 NM_001126121.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1533648).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A19	NM_001126121.2	MANE Select	c.789G>T	p.Lys263Asn	missense	Exon 8 of 8	NP_001119593.1
	SLC25A19	NM_001126122.2		c.789G>T	p.Lys263Asn	missense	Exon 7 of 7	NP_001119594.1
	SLC25A19	NM_021734.5		c.789G>T	p.Lys263Asn	missense	Exon 8 of 8	NP_068380.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A19	ENST00000416858.7	TSL:1 MANE Select	c.789G>T	p.Lys263Asn	missense	Exon 8 of 8	ENSP00000397818.2
	SLC25A19	ENST00000402418.7	TSL:1	c.789G>T	p.Lys263Asn	missense	Exon 6 of 6	ENSP00000385312.3
	SLC25A19	ENST00000320362.7	TSL:2	c.789G>T	p.Lys263Asn	missense	Exon 9 of 9	ENSP00000319574.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	3.8
DANN	Benign	0.65
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.33	N
PhyloP100		-0.028
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.22
Sift	Benign	0.33	T
Sift4G	Benign	0.84	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.54		Loss of MoRF binding (P = 0.0301)
MVP		0.38
MPC		0.17
ClinPred		0.79	D
GERP RS		3.1
Varity_R		0.031
gMVP		0.65

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: rs797045968; hg19: chr17-73269706;