Genetic Variant NM_207348.3:c.304C>G (chr1-15736789-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207348.3(SLC25A34):c.304C>G(p.Gln102Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC25A34
NM_207348.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.187

Variant links:

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]

SLC25A34 links:

ENSG00000237938 (HGNC:):

ENSG00000237938 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.069788605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A34	NM_207348.3 link	c.304C>G	p.Gln102Glu	missense_variant	Exon 1 of 5	ENST00000294454.6	NP_997231.1	Q6PIV7
SLC25A34	XM_017001083.2 link	c.304C>G	p.Gln102Glu	missense_variant	Exon 1 of 4		XP_016856572.1
SLC25A34	XM_011541293.2 link	c.304C>G	p.Gln102Glu	missense_variant	Exon 1 of 5		XP_011539595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A34	ENST00000294454.6 link	c.304C>G	p.Gln102Glu	missense_variant	Exon 1 of 5	1	NM_207348.3	ENSP00000294454.5		Q6PIV7
ENSG00000237938	ENST00000453804.1 link	n.36+72G>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.304C>G (p.Q102E) alteration is located in exon 1 (coding exon 1) of the SLC25A34 gene. This alteration results from a C to G substitution at nucleotide position 304, causing the glutamine (Q) at amino acid position 102 to be replaced by a glutamic acid (E). 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

Benign

0.099

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.7

DANN

Benign

0.57

DEOGEN2

Benign

0.010

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.67

M_CAP

Benign

0.028

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.40

PROVEAN

Benign

0.37

REVEL

Benign

0.16

Sift

Benign

0.097

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.30

MutPred

0.28

Gain of disorder (P = 0.1154);

MVP

0.24

MPC

0.073

ClinPred

0.15

GERP RS

1.9

Varity_R

0.069

gMVP

0.40

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over