chr2-171785280-AGTGGCTGCCACTGCTGCCTTTGGCTGAACCACAGCAACACTAGGAGACTTAAATTTCGGGAGATAAAGGCCAAATTTGTTTTCGATGCCTGCAAAC-A

Variant names:

• chr2-171785280-AGTGGCTGCCACTGCTGCCTTTGGCTGAACCACAGCAACACTAGGAGACTTAAATTTCGGGAGATAAAGGCCAAATTTGTTTTCGATGCCTGCAAAC-A
• rs2105829329
• NM_003705.5:c.1935_2030delGTTTGCAGGCATCGAAAACAAATTTGGCCTTTATCTCCCGAAATTTAAGTCTCCTAGTGTTGCTGTGGTTCAGCCAAAGGCAGCAGTGGCAGCCAC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_003705.5(SLC25A12):​c.1935_2030delGTTTGCAGGCATCGAAAACAAATTTGGCCTTTATCTCCCGAAATTTAAGTCTCCTAGTGTTGCTGTGGTTCAGCCAAAGGCAGCAGTGGCAGCCAC​(p.Phe646_Thr677del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T645T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A12 NM_003705.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18
• Publications: 0 publications found

Genes affected

SLC25A12 (HGNC:10982): (solute carrier family 25 member 12) This gene encodes a calcium-binding mitochondrial carrier protein. The encoded protein localizes to the mitochondria and is involved in the exchange of aspartate for glutamate across the inner mitochondrial membrane. Polymorphisms in this gene may be associated with autism, and mutations in this gene may also be a cause of global cerebral hypomyelination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]

SLC25A12 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 39

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_003705.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003705.5. 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
	SLC25A12	NM_003705.5	MANE Select	c.1935_2030delGTTTGCAGGCATCGAAAACAAATTTGGCCTTTATCTCCCGAAATTTAAGTCTCCTAGTGTTGCTGTGGTTCAGCCAAAGGCAGCAGTGGCAGCCAC	p.Phe646_Thr677del	disruptive_inframe_deletion	Exon 18 of 18	NP_003696.2
	SLC25A12	NR_047549.2		n.1849_1944delGTTTGCAGGCATCGAAAACAAATTTGGCCTTTATCTCCCGAAATTTAAGTCTCCTAGTGTTGCTGTGGTTCAGCCAAAGGCAGCAGTGGCAGCCAC		non_coding_transcript_exon	Exon 17 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A12	ENST00000422440.7	TSL:1 MANE Select	c.1935_2030delGTTTGCAGGCATCGAAAACAAATTTGGCCTTTATCTCCCGAAATTTAAGTCTCCTAGTGTTGCTGTGGTTCAGCCAAAGGCAGCAGTGGCAGCCAC	p.Phe646_Thr677del	disruptive_inframe_deletion	Exon 18 of 18	ENSP00000388658.2	O75746-1
	SLC25A12	ENST00000958780.1		c.2112_2207delGTTTGCAGGCATCGAAAACAAATTTGGCCTTTATCTCCCGAAATTTAAGTCTCCTAGTGTTGCTGTGGTTCAGCCAAAGGCAGCAGTGGCAGCCAC	p.Phe705_Thr736del	disruptive_inframe_deletion	Exon 20 of 20	ENSP00000628839.1
	SLC25A12	ENST00000958781.1		c.2022_2117delGTTTGCAGGCATCGAAAACAAATTTGGCCTTTATCTCCCGAAATTTAAGTCTCCTAGTGTTGCTGTGGTTCAGCCAAAGGCAGCAGTGGCAGCCAC	p.Phe675_Thr706del	disruptive_inframe_deletion	Exon 19 of 19	ENSP00000628840.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

Splicing

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

Other links and lift over

dbSNP: rs2105829329; hg19: chr2-172641790;