5-110738976-T-G

Position:

• chr5-110738976-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001303250.3(SLC25A46):​c.10+729T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,454,162 control chromosomes in the GnomAD database, including 5,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (600 hom., cov: 32)
  • Exomes 𝑓: 0.085 (4995 hom.)
• Consequence: SLC25A46 NM_001303250.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0930

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]

TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 5-110738976-T-G is Benign according to our data. Variant chr5-110738976-T-G is described in ClinVar as [Benign]. Clinvar id is 1284005.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A46	NM_138773.4			upstream_gene_variant		ENST00000355943.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A46	ENST00000513807.5	c.-204+729T>G		intron_variant		2
SLC25A46	ENST00000508781.5	n.112+729T>G		intron_variant, non_coding_transcript_variant		4
SLC25A46	ENST00000355943.8			upstream_gene_variant		1	NM_138773.4	P1
TMEM232	ENST00000515278.6			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13196 AN: 152192 Hom.: 598 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0812

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0861

GnomAD4 exome AF: 0.0854 AC: 111135 AN: 1301852 Hom.: 4995 Cov.: 31 AF XY: 0.0841 AC XY: 53395 AN XY: 635028

Gnomad4 AFR exome AF: 0.0684

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.0786

Gnomad4 EAS exome AF: 0.0234

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.0926

Gnomad4 NFE exome AF: 0.0902

Gnomad4 OTH exome AF: 0.0835

GnomAD4 genome AF: 0.0867 AC: 13211 AN: 152310 Hom.: 600 Cov.: 32 AF XY: 0.0872 AC XY: 6493 AN XY: 74494

Gnomad4 AFR AF: 0.0731

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0812

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.0921

Gnomad4 NFE AF: 0.0935

Gnomad4 OTH AF: 0.0843

Alfa AF: 0.0661 Hom.: 126

Bravo AF: 0.0913

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.0
DANN	Benign	0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17132319; hg19: chr5-110074677; COSMIC: COSV63506692; COSMIC: COSV63506692;