17-4937791-A-C

Variant names:

• chr17-4937791-A-C
• NM_003562.5:c.895T>G

Variant summary

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

The NM_003562.5(SLC25A11):​c.895T>G​(p.Phe299Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A11 NM_003562.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.53
• Publications: 0 publications found

Genes affected

SLC25A11 (HGNC:10981): (solute carrier family 25 member 11) The oxoglutarate/malate carrier transports 2-oxoglutarate across the inner membranes of mitochondria in an electroneutral exchange for malate or other dicarboxylic acids (summary by Iacobazzi et al., 1992 [PubMed 1457818]).[supplied by OMIM, Jan 2011]

SLC25A11 Gene-Disease associations (from GenCC):

• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pheochromocytoma/paraganglioma syndrome 6

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003562.5. 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
	SLC25A11	NM_003562.5	MANE Select	c.895T>G	p.Phe299Val	missense	Exon 8 of 8	NP_003553.2
	SLC25A11	NM_001165417.2		c.862T>G	p.Phe288Val	missense	Exon 8 of 8	NP_001158889.1
	SLC25A11	NM_001165418.2		c.742T>G	p.Phe248Val	missense	Exon 7 of 7	NP_001158890.1	Q02978-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A11	ENST00000225665.12	TSL:1 MANE Select	c.895T>G	p.Phe299Val	missense	Exon 8 of 8	ENSP00000225665.7	Q02978-1
	SLC25A11	ENST00000940187.1		c.979T>G	p.Phe327Val	missense	Exon 7 of 7	ENSP00000610246.1
	SLC25A11	ENST00000576951.1	TSL:5	c.862T>G	p.Phe288Val	missense	Exon 8 of 8	ENSP00000458993.1	I3L1P8

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	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.8	L
PhyloP100		8.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.017	D
Polyphen		0.20	B
Vest4		0.72
MutPred		0.46		Gain of sheet (P = 0.0827)
MVP		0.79
MPC		1.3
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.59
gMVP		0.97

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

hg19: chr17-4841086;