1-15736544-C-T

Variant names:

• chr1-15736544-C-T
• rs1019517996
• NM_207348.3:c.59C>T

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.59C>T​(p.Ala20Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000023 in 1,302,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. A20G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: SLC25A34 NM_207348.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• 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]

ENSG00000237938 (HGNC:58402):

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, 0.939

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.59C>T	p.Ala20Val	missense	Exon 1 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.59C>T	p.Ala20Val	missense	Exon 1 of 5	ENSP00000294454.5	Q6PIV7
	SLC25A34	ENST00000949755.1		c.59C>T	p.Ala20Val	missense	Exon 1 of 5	ENSP00000619814.1
	SLC25A34	ENST00000852312.1		c.59C>T	p.Ala20Val	missense	Exon 1 of 4	ENSP00000522371.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000230 AC: 3 AN: 1302408 Hom.: 0 Cov.: 31 AF XY: 0.00000316 AC XY: 2 AN XY: 632630

African (AFR) AF: 0.00 AC: 0 AN: 28242

American (AMR) AF: 0.00 AC: 0 AN: 20870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19006

East Asian (EAS) AF: 0.00 AC: 0 AN: 34300

South Asian (SAS) AF: 0.00 AC: 0 AN: 63428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3900

European-Non Finnish (NFE) AF: 0.00000290 AC: 3 AN: 1035128

Other (OTH) AF: 0.00 AC: 0 AN: 53546

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.78		Loss of helix (P = 0.1299)
MVP		0.75
MPC		0.37
ClinPred		1.0	D
GERP RS		3.8
PromoterAI		0.0058	Neutral
Varity_R		0.72
gMVP		0.86
Mutation Taster		=12/88	disease causing

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: rs1019517996; hg19: chr1-16063039;