chr5-110746300-C-T

Position:

• chr5-110746300-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138773.4(SLC25A46):​c.416C>T​(p.Thr139Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC25A46 NM_138773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14

Genes affected

SLC25A46 (HGNC:25198): (solute carrier family 25 member 46) This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]

SLC25A46 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A46	NM_138773.4	c.416C>T	p.Thr139Ile	missense_variant	4/8	ENST00000355943.8	NP_620128.1
SLC25A46	NM_001303249.3	c.416C>T	p.Thr139Ile	missense_variant	4/8		NP_001290178.1
SLC25A46	NM_001303250.3	c.143C>T	p.Thr48Ile	missense_variant	4/8		NP_001290179.1
SLC25A46	NR_138151.2	n.529C>T		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A46	ENST00000355943.8	c.416C>T	p.Thr139Ile	missense_variant	4/8	1	NM_138773.4	ENSP00000348211.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.48
Sift	Benign	0.45	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.88	P;.
Vest4		0.66
MutPred		0.43		Loss of catalytic residue at T139 (P = 0.1532);Loss of catalytic residue at T139 (P = 0.1532);
MVP		0.74
MPC		0.18
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs202123515; hg19: chr5-110082001;