1-9567286-C-G

Variant names:

• chr1-9567286-C-G
• rs373779347
• NM_032315.3:c.239C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032315.3(SLC25A33):​c.239C>G​(p.Ser80Trp) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S80T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A33 NM_032315.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69
• Publications: 0 publications found

Genes affected

SLC25A33 (HGNC:29681): (solute carrier family 25 member 33) SLC25A33 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032315.3. 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
	SLC25A33	NM_032315.3	MANE Select	c.239C>G	p.Ser80Trp	missense splice_region	Exon 3 of 7	NP_115691.1	Q9BSK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A33	ENST00000302692.7	TSL:1 MANE Select	c.239C>G	p.Ser80Trp	missense splice_region	Exon 3 of 7	ENSP00000306328.5	Q9BSK2
	SLC25A33	ENST00000891101.1		c.239C>G	p.Ser80Trp	missense splice_region	Exon 3 of 7	ENSP00000561160.1
	SLC25A33	ENST00000891098.1		c.239C>G	p.Ser80Trp	missense splice_region	Exon 3 of 7	ENSP00000561157.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250990 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Benign	0.28
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.54
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.49		Loss of disorder (P = 0.0062)
MVP		0.79
MPC		1.5
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.91
Mutation Taster		=70/30	polymorphism

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: rs373779347; hg19: chr1-9627344;