5-110738976-T-G

Variant names:

• chr5-110738976-T-G
• rs17132319
• NM_001303250.3:c.10+729T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.47).
• BP6: Variant 5-110738976-T-G is Benign according to our data. Variant chr5-110738976-T-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303250.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A46	NM_001303250.3		c.10+729T>G		intron	N/A	NP_001290179.1	B4DY98
	SLC25A46	NM_138773.4	MANE Select	c.-144T>G		upstream_gene	N/A	NP_620128.1	Q96AG3-1
	SLC25A46	NM_001303249.3		c.-144T>G		upstream_gene	N/A	NP_001290178.1	Q96AG3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A46	ENST00000513807.5	TSL:2	c.-204+729T>G		intron	N/A	ENSP00000421134.1	E7EVY2
	SLC25A46	ENST00000508781.5	TSL:4	n.112+729T>G		intron	N/A
	SLC25A46	ENST00000355943.8	TSL:1 MANE Select	c.-144T>G		upstream_gene	N/A	ENSP00000348211.3	Q96AG3-1

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

African (AFR) AF: 0.0684 AC: 1942 AN: 28384

American (AMR) AF: 0.126 AC: 2592 AN: 20534

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 1572 AN: 19998

East Asian (EAS) AF: 0.0234 AC: 817 AN: 34912

South Asian (SAS) AF: 0.0364 AC: 2359 AN: 64850

European-Finnish (FIN) AF: 0.0926 AC: 2957 AN: 31918

Middle Eastern (MID) AF: 0.0758 AC: 281 AN: 3708

European-Non Finnish (NFE) AF: 0.0902 AC: 94083 AN: 1043250

Other (OTH) AF: 0.0835 AC: 4532 AN: 54298

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

African (AFR) AF: 0.0731 AC: 3039 AN: 41572

American (AMR) AF: 0.126 AC: 1930 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 282 AN: 3472

East Asian (EAS) AF: 0.0249 AC: 129 AN: 5188

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4832

European-Finnish (FIN) AF: 0.0921 AC: 979 AN: 10624

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6361 AN: 68004

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0760 Hom.: 237

Bravo AF: 0.0913

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.0
DANN	Benign	0.89
PhyloP100		0.093
PromoterAI		-0.32	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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