5-110738696-T-C

Position:

• chr5-110738696-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001303250.3(SLC25A46):​c.10+449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 228,832 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (43 hom., cov: 32)
  • Exomes 𝑓: 0.015 (17 hom.)
• Consequence: SLC25A46 NM_001303250.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0750

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-110738696-T-C is Benign according to our data. Variant chr5-110738696-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1219661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0231 (3509/151998) while in subpopulation AFR AF= 0.0283 (1175/41488). AF 95% confidence interval is 0.027. There are 43 homozygotes in gnomad4. There are 1706 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A46	NM_001303250.3	c.10+449T>C		intron_variant
TMEM232	XM_006714670.4	c.-298+26A>G		intron_variant
TMEM232	XM_011543552.3	c.-649+26A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A46	ENST00000513807.5	c.-204+449T>C		intron_variant		2
TMEM232	ENST00000515278.6	c.-298+26A>G		intron_variant		5
TMEM232	ENST00000503527.6	n.197+26A>G		intron_variant, non_coding_transcript_variant		3
SLC25A46	ENST00000508781.5	n.112+449T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3509 AN: 151878 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00931

Gnomad SAS AF: 0.00563

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.0149 AC: 1144 AN: 76834 Hom.: 17 Cov.: 0 AF XY: 0.0139 AC XY: 565 AN XY: 40686

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.00780

Gnomad4 EAS exome AF: 0.00685

Gnomad4 SAS exome AF: 0.00785

Gnomad4 FIN exome AF: 0.0259

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0181

GnomAD4 genome AF: 0.0231 AC: 3509 AN: 151998 Hom.: 43 Cov.: 32 AF XY: 0.0230 AC XY: 1706 AN XY: 74276

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00933

Gnomad4 SAS AF: 0.00564

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.00957 Hom.: 4

Bravo AF: 0.0219

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116525996; hg19: chr5-110074397;