17-75273177-G-C

Variant names:

• chr17-75273177-G-C
• rs7198
• NM_001126121.2:c.*274C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001126121.2(SLC25A19):​c.*274C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 476,366 control chromosomes in the GnomAD database, including 103,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (27210 hom., cov: 32)
  • Exomes 𝑓: 0.67 (76121 hom.)
• Consequence: SLC25A19 NM_001126121.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.833
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-75273177-G-C is Benign according to our data. Variant chr17-75273177-G-C is described in ClinVar as Benign. ClinVar VariationId is 325062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

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.*274C>G		3_prime_UTR	Exon 8 of 8	NP_001119593.1
	SLC25A19	NM_001126122.2		c.*274C>G		3_prime_UTR	Exon 7 of 7	NP_001119594.1
	SLC25A19	NM_021734.5		c.*274C>G		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.*274C>G		3_prime_UTR	Exon 8 of 8	ENSP00000397818.2
	SLC25A19	ENST00000402418.7	TSL:1	c.*274C>G		3_prime_UTR	Exon 6 of 6	ENSP00000385312.3
	SLC25A19	ENST00000320362.7	TSL:2	c.*274C>G		3_prime_UTR	Exon 9 of 9	ENSP00000319574.3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82523 AN: 152008 Hom.: 27214 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.539

GnomAD4 exome AF: 0.673 AC: 218314 AN: 324240 Hom.: 76121 Cov.: 2 AF XY: 0.671 AC XY: 115705 AN XY: 172360

African (AFR) AF: 0.144 AC: 1401 AN: 9696

American (AMR) AF: 0.693 AC: 9976 AN: 14392

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 5570 AN: 9798

East Asian (EAS) AF: 0.878 AC: 17279 AN: 19676

South Asian (SAS) AF: 0.645 AC: 27894 AN: 43258

European-Finnish (FIN) AF: 0.776 AC: 13042 AN: 16806

Middle Eastern (MID) AF: 0.491 AC: 697 AN: 1420

European-Non Finnish (NFE) AF: 0.685 AC: 130644 AN: 190770

Other (OTH) AF: 0.641 AC: 11811 AN: 18424

GnomAD4 genome AF: 0.542 AC: 82519 AN: 152126 Hom.: 27210 Cov.: 32 AF XY: 0.552 AC XY: 41042 AN XY: 74368

African (AFR) AF: 0.147 AC: 6114 AN: 41514

American (AMR) AF: 0.648 AC: 9883 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3470

East Asian (EAS) AF: 0.855 AC: 4423 AN: 5172

South Asian (SAS) AF: 0.632 AC: 3046 AN: 4816

European-Finnish (FIN) AF: 0.786 AC: 8323 AN: 10590

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46786 AN: 67984

Other (OTH) AF: 0.540 AC: 1142 AN: 2116

Alfa AF: 0.613 Hom.: 3959

Bravo AF: 0.520

Asia WGS AF: 0.652 AC: 2270 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Amish lethal microcephaly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.1
DANN	Benign	0.69
PhyloP100		-0.83
Mutation Taster		=99/1	polymorphism (auto)

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: rs7198; hg19: chr17-73269258;