5-110738678-T-C

Variant names:

• chr5-110738678-T-C
• rs150439637
• NM_001303250.3:c.10+431T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A46	NM_001303250.3	c.10+431T>C		intron_variant	Intron 1 of 7		NP_001290179.1
TMEM232	XM_006714670.4	c.-298+44A>G		intron_variant	Intron 1 of 15		XP_006714733.1
TMEM232	XM_011543552.3	c.-649+44A>G		intron_variant	Intron 1 of 16		XP_011541854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A46	ENST00000513807.5	c.-204+431T>C		intron_variant	Intron 1 of 7	2		ENSP00000421134.1
TMEM232	ENST00000515278.6	c.-298+44A>G		intron_variant	Intron 1 of 6	5		ENSP00000421614.2
TMEM232	ENST00000503527.6	n.197+44A>G		intron_variant	Intron 1 of 3	3
SLC25A46	ENST00000508781.5	n.112+431T>C		intron_variant	Intron 1 of 7	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

African (AFR) AF: 0.0114 AC: 8 AN: 704

American (AMR) AF: 0.00 AC: 0 AN: 2154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1942

East Asian (EAS) AF: 0.00 AC: 0 AN: 784

South Asian (SAS) AF: 0.0000713 AC: 1 AN: 14018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46480

Other (OTH) AF: 0.000907 AC: 4 AN: 4410

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

African (AFR) AF: 0.0238 AC: 989 AN: 41528

American (AMR) AF: 0.00131 AC: 20 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67992

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

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

Jul 15, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.60
DANN	Benign	0.68
PhyloP100		-0.86
PromoterAI		0.14	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs150439637; hg19: chr5-110074379;