1-15738212-C-G

Variant names:

• chr1-15738212-C-G
• NM_207348.3:c.564C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_207348.3(SLC25A34):​c.564C>G​(p.Phe188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: -0.0170

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A34	NM_207348.3	c.564C>G	p.Phe188Leu	missense_variant	Exon 3 of 5	ENST00000294454.6	NP_997231.1
SLC25A34	XM_017001083.2	c.564C>G	p.Phe188Leu	missense_variant	Exon 3 of 4		XP_016856572.1
SLC25A34	XM_011541293.2	c.564C>G	p.Phe188Leu	missense_variant	Exon 3 of 5		XP_011539595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A34	ENST00000294454.6	c.564C>G	p.Phe188Leu	missense_variant	Exon 3 of 5	1	NM_207348.3	ENSP00000294454.5
SLC25A34	ENST00000489568.1	n.332C>G		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.564C>G (p.F188L) alteration is located in exon 3 (coding exon 3) of the SLC25A34 gene. This alteration results from a C to G substitution at nucleotide position 564, causing the phenylalanine (F) at amino acid position 188 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.62		Gain of helix (P = 0.0425);
MVP		0.55
MPC		0.39
ClinPred		1.0	D
GERP RS		-3.1
Varity_R		0.71
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16064707;