chr1-15738151-A-C

Variant names:

• chr1-15738151-A-C
• rs781268915
• NM_207348.3:c.503A>C

Variant summary

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

The NM_207348.3(SLC25A34):​c.503A>C​(p.Gln168Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,736 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q168R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A34 NM_207348.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32
• 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 2 ACMG points.

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

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.503A>C	p.Gln168Pro	missense	Exon 3 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.503A>C	p.Gln168Pro	missense	Exon 3 of 5	ENSP00000294454.5	Q6PIV7
	SLC25A34	ENST00000949755.1		c.503A>C	p.Gln168Pro	missense	Exon 3 of 5	ENSP00000619814.1
	SLC25A34	ENST00000852312.1		c.437A>C	p.Gln146Pro	missense	Exon 2 of 4	ENSP00000522371.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455736 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723466

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25768

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108428

Other (OTH) AF: 0.00 AC: 0 AN: 60118

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.3
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.0010	B
Vest4		0.52
MutPred		0.81		Loss of MoRF binding (P = 0.0285)
MVP		0.38
MPC		0.089
ClinPred		0.86	D
GERP RS		3.4
Varity_R		0.76
gMVP		0.95
Mutation Taster		=75/25	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: rs781268915; hg19: chr1-16064646;