rs1555922652

Variant names:

• chr22-19177191-T-G
• rs1555922652
• NM_005984.5:c.455A>C

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_005984.5(SLC25A1):​c.455A>C​(p.His152Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A1 NM_005984.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09
• Publications: 0 publications found

Genes affected

SLC25A1 (HGNC:10979): (solute carrier family 25 member 1) This gene encodes a member of the mitochondrial carrier subfamily of solute carrier proteins. Members of this family include nuclear-encoded transporters that translocate small metabolites across the mitochondrial membrane. This protein regulates the movement of citrate across the inner membranes of the mitochondria. Mutations in this gene have been associated with combined D-2- and L-2-hydroxyglutaric aciduria. Pseudogenes of this gene have been identified on chromosomes 7, 11, 16, and 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

LINC01311 (HGNC:50503): (long intergenic non-protein coding RNA 1311)

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM1: In a chain Tricarboxylate transport protein, mitochondrial (size 297) in uniprot entity TXTP_HUMAN there are 11 pathogenic changes around while only 0 benign (100%) in NM_005984.5
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005984.5. 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
	SLC25A1	NM_005984.5	MANE Select	c.455A>C	p.His152Pro	missense	Exon 5 of 9	NP_005975.1	P53007
	SLC25A1	NM_001256534.2		c.476A>C	p.His159Pro	missense	Exon 4 of 8	NP_001243463.1	D9HTE9
	SLC25A1	NM_001287387.2		c.146A>C	p.His49Pro	missense	Exon 5 of 9	NP_001274316.1	D3DX16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A1	ENST00000215882.10	TSL:1 MANE Select	c.455A>C	p.His152Pro	missense	Exon 5 of 9	ENSP00000215882.5	P53007
	SLC25A1	ENST00000880508.1		c.494A>C	p.His165Pro	missense	Exon 5 of 9	ENSP00000550567.1
	SLC25A1	ENST00000880513.1		c.464A>C	p.His155Pro	missense	Exon 5 of 9	ENSP00000550572.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Benign	0.95
DEOGEN2	Uncertain	0.63	D
Eigen	Benign	0.074
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.014	D
Sift4G	Benign	0.16	T
Polyphen		0.12	B
Vest4		0.71
MutPred		0.69		Loss of sheet (P = 0.1158)
MVP		0.88
MPC		0.79
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.97
gMVP		0.97
Mutation Taster		=27/73	disease causing

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: rs1555922652; hg19: chr22-19164704;