rs960197684

Positions:

• chr5-110739142-G-A
• chr5-110739142-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138773.4(SLC25A46):​c.23G>A​(p.Gly8Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000788 in 1,396,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: SLC25A46 NM_138773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.41

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16188315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A46	NM_138773.4	c.23G>A	p.Gly8Glu	missense_variant	1/8	ENST00000355943.8	NP_620128.1
SLC25A46	NM_001303249.3	c.23G>A	p.Gly8Glu	missense_variant	1/8		NP_001290178.1
SLC25A46	NM_001303250.3	c.10+895G>A		intron_variant			NP_001290179.1
SLC25A46	NR_138151.2	n.136G>A		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A46	ENST00000355943.8	c.23G>A	p.Gly8Glu	missense_variant	1/8	1	NM_138773.4	ENSP00000348211.3
SLC25A46	ENST00000447245.6	c.23G>A	p.Gly8Glu	missense_variant	1/8	2		ENSP00000399717.2
SLC25A46	ENST00000513807.5	c.-204+895G>A		intron_variant		2		ENSP00000421134.1
SLC25A46	ENST00000508781.5	n.112+895G>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000658 AC: 1 AN: 152030 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 80958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000173

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000788 AC: 11 AN: 1396802 Hom.: 0 Cov.: 31 AF XY: 0.00000871 AC XY: 6 AN XY: 688978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000927

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.093
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.028	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		0.0	B;.
Vest4		0.15
MutPred		0.13		Gain of solvent accessibility (P = 0.1683);Gain of solvent accessibility (P = 0.1683);
MVP		0.68
MPC		0.15
ClinPred		0.91	D
GERP RS		4.0
Varity_R		0.36
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

Other links and lift over

dbSNP: rs960197684; hg19: chr5-110074843;