chr5-110739161-C-G

Position:

• chr5-110739161-C-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_138773.4(SLC25A46):​c.42C>G​(p.Tyr14Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y14Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A46 NM_138773.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.575

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 24 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-110739161-C-G is Pathogenic according to our data. Variant chr5-110739161-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1068768.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A46	NM_138773.4	c.42C>G	p.Tyr14Ter	stop_gained	1/8	ENST00000355943.8
SLC25A46	NM_001303249.3	c.42C>G	p.Tyr14Ter	stop_gained	1/8
SLC25A46	NM_001303250.3	c.10+914C>G		intron_variant
SLC25A46	NR_138151.2	n.155C>G		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A46	ENST00000355943.8	c.42C>G	p.Tyr14Ter	stop_gained	1/8	1	NM_138773.4	P1
SLC25A46	ENST00000447245.6	c.42C>G	p.Tyr14Ter	stop_gained	1/8	2
SLC25A46	ENST00000513807.5	c.-204+914C>G		intron_variant		2
SLC25A46	ENST00000508781.5	n.112+914C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Pontocerebellar hypoplasia, type 1E Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.65	D
MutationTaster	Benign	1.0	A;A;D;D
Vest4		0.24
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: chr5-110074862;