NM_207348.3:c.383A>C

Variant names:

• chr1-15737933-A-C
• NM_207348.3:c.383A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_207348.3(SLC25A34):​c.383A>C​(p.Lys128Thr) 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: SLC25A34 NM_207348.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28
• Publications: 0 publications found

Genes affected

SLC25A34 (HGNC:27653): (solute carrier family 25 member 34) SLC25A34 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207348.3. 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
	SLC25A34	NM_207348.3	MANE Select	c.383A>C	p.Lys128Thr	missense	Exon 2 of 5	NP_997231.1	Q6PIV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A34	ENST00000294454.6	TSL:1 MANE Select	c.383A>C	p.Lys128Thr	missense	Exon 2 of 5	ENSP00000294454.5	Q6PIV7
	SLC25A34	ENST00000949755.1		c.383A>C	p.Lys128Thr	missense	Exon 2 of 5	ENSP00000619814.1
	SLC25A34	ENST00000852313.1		c.383A>C	p.Lys128Thr	missense	Exon 2 of 4	ENSP00000522372.1

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	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.85	P
Vest4		0.55
MutPred		0.81		Gain of glycosylation at T129 (P = 0.0346)
MVP		0.71
MPC		0.39
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.75
gMVP		0.90
Mutation Taster		=52/48	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

hg19: chr1-16064428;