5-110739127-CGCG-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_138773.4(SLC25A46):c.12_14del(p.Arg5del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P3P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A46 NM_138773.4 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_138773.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A46	NM_138773.4	c.12_14del	p.Arg5del	inframe_deletion	1/8	ENST00000355943.8
SLC25A46	NM_001303249.3	c.12_14del	p.Arg5del	inframe_deletion	1/8
SLC25A46	NM_001303250.3	c.10+884_10+886del		intron_variant
SLC25A46	NR_138151.2	n.125_127del		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A46	ENST00000355943.8	c.12_14del	p.Arg5del	inframe_deletion	1/8	1	NM_138773.4	P1
SLC25A46	ENST00000447245.6	c.12_14del	p.Arg5del	inframe_deletion	1/8	2
SLC25A46	ENST00000513807.5	c.-204+884_-204+886del		intron_variant		2
SLC25A46	ENST00000508781.5	n.112+884_112+886del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neuropathy, hereditary motor and sensory, type 6B Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jul 10, 2021

This variant, c.12_14del, results in the deletion of 1 amino acid(s) of the SLC25A46 protein (p.Arg5del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SLC25A46-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-110074828;