rs1410055577

Variant names:

• chr5-110739313-G-A
• NM_138773.4:c.194G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-110739313-G-A
• chr5-110739313-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138773.4(SLC25A46):​c.194G>A​(p.Gly65Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,417,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SLC25A46 NM_138773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15327638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A46	NM_138773.4	c.194G>A	p.Gly65Asp	missense_variant	Exon 1 of 8	ENST00000355943.8	NP_620128.1
SLC25A46	NM_001303249.3	c.194G>A	p.Gly65Asp	missense_variant	Exon 1 of 8		NP_001290178.1
SLC25A46	NM_001303250.3	c.10+1066G>A		intron_variant	Intron 1 of 7		NP_001290179.1
SLC25A46	NR_138151.2	n.307G>A		non_coding_transcript_exon_variant	Exon 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A46	ENST00000355943.8	c.194G>A	p.Gly65Asp	missense_variant	Exon 1 of 8	1	NM_138773.4	ENSP00000348211.3
SLC25A46	ENST00000447245.6	c.194G>A	p.Gly65Asp	missense_variant	Exon 1 of 8	2		ENSP00000399717.2
SLC25A46	ENST00000513807.5	c.-204+1066G>A		intron_variant	Intron 1 of 7	2		ENSP00000421134.1
SLC25A46	ENST00000508781.5	n.112+1066G>A		intron_variant	Intron 1 of 7	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1417426 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 700996

Gnomad4 AFR exome AF: 0.0000306

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0053	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.73	T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.15	N;N
REVEL	Benign	0.20
Sift	Benign	0.064	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.23	B;.
Vest4		0.11
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP		0.61
MPC		0.17
ClinPred		0.52	D
GERP RS		3.3
Varity_R		0.067
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-110075014;