chr5-110739114-G-C

Variant names:

• chr5-110739114-G-C
• rs753376360
• NM_138773.4:c.-6G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138773.4(SLC25A46):​c.-6G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SLC25A46 NM_138773.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138773.4. 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_138773.4	MANE Select	c.-6G>C		5_prime_UTR	Exon 1 of 8	NP_620128.1	Q96AG3-1
	SLC25A46	NM_001303249.3		c.-6G>C		5_prime_UTR	Exon 1 of 8	NP_001290178.1	Q96AG3-3
	SLC25A46	NM_001303250.3		c.10+867G>C		intron	N/A	NP_001290179.1	B4DY98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A46	ENST00000355943.8	TSL:1 MANE Select	c.-6G>C		5_prime_UTR	Exon 1 of 8	ENSP00000348211.3	Q96AG3-1
	SLC25A46	ENST00000923605.1		c.-6G>C		5_prime_UTR	Exon 1 of 8	ENSP00000593664.1
	SLC25A46	ENST00000447245.6	TSL:2	c.-6G>C		5_prime_UTR	Exon 1 of 8	ENSP00000399717.2	Q96AG3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393470 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 687400

African (AFR) AF: 0.00 AC: 0 AN: 31474

American (AMR) AF: 0.00 AC: 0 AN: 35606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25116

East Asian (EAS) AF: 0.00 AC: 0 AN: 35658

South Asian (SAS) AF: 0.00 AC: 0 AN: 79100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4500

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078398

Other (OTH) AF: 0.00 AC: 0 AN: 57798

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		-0.73
PromoterAI		0.040	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs753376360; hg19: chr5-110074815;