5-110738678-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001303250.3(SLC25A46):c.10+431T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 227,794 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: SLC25A46 NM_001303250.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.859

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=-0.8).
• BP6: Variant 5-110738678-T-C is Benign according to our data. Variant chr5-110738678-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1187279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00669 (1018/152172) while in subpopulation AFR AF= 0.0238 (989/41528). AF 95% confidence interval is 0.0226. There are 16 homozygotes in gnomad4. There are 465 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A46	NM_001303250.3	c.10+431T>C		intron_variant
TMEM232	XM_006714670.4	c.-298+44A>G		intron_variant
TMEM232	XM_011543552.3	c.-649+44A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A46	ENST00000513807.5	c.-204+431T>C		intron_variant		2
TMEM232	ENST00000515278.6	c.-298+44A>G		intron_variant		5
TMEM232	ENST00000503527.6	n.197+44A>G		intron_variant, non_coding_transcript_variant		3
SLC25A46	ENST00000508781.5	n.112+431T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00667 AC: 1014 AN: 152054 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000172 AC: 13 AN: 75622 Hom.: 0 Cov.: 0 AF XY: 0.000150 AC XY: 6 AN XY: 40106

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000713

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000907

GnomAD4 genome AF: 0.00669 AC: 1018 AN: 152172 Hom.: 16 Cov.: 32 AF XY: 0.00625 AC XY: 465 AN XY: 74398

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00562 Hom.: 1

Bravo AF: 0.00762

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.60
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs150439637; hg19: chr5-110074379;