rs763593018

Variant names:

• chr4-185143432-C-A
• rs763593018
• NM_001151.4:c.60C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-185143432-C-A
• chr4-185143432-C-G
• chr4-185143432-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001151.4(SLC25A4):​c.60C>A​(p.Ala20Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A4 NM_001151.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.486
• Publications: 0 publications found

Genes affected

SLC25A4 (HGNC:10990): (solute carrier family 25 member 4) This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Mutations in this gene have been shown to result in autosomal dominant progressive external opthalmoplegia and familial hypertrophic cardiomyopathy. [provided by RefSeq, Jun 2013]

SLC25A4 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Fontaine progeroid syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P
• mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant progressive external ophthalmoplegia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Sengers syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 4-185143432-C-A is Benign according to our data. Variant chr4-185143432-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2581490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.486 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001151.4. 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
	SLC25A4	NM_001151.4	MANE Select	c.60C>A	p.Ala20Ala	synonymous	Exon 1 of 4	NP_001142.2	A0A0S2Z3H3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A4	ENST00000281456.11	TSL:1 MANE Select	c.60C>A	p.Ala20Ala	synonymous	Exon 1 of 4	ENSP00000281456.5	P12235
	SLC25A4	ENST00000948444.1		c.60C>A	p.Ala20Ala	synonymous	Exon 1 of 4	ENSP00000618503.1
	SLC25A4	ENST00000948442.1		c.60C>A	p.Ala20Ala	synonymous	Exon 1 of 4	ENSP00000618501.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000739 AC: 1 AN: 135232 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1367768 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 674654

African (AFR) AF: 0.00 AC: 0 AN: 28830

American (AMR) AF: 0.00 AC: 0 AN: 32878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24144

East Asian (EAS) AF: 0.00 AC: 0 AN: 32676

South Asian (SAS) AF: 0.00 AC: 0 AN: 76254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5436

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063032

Other (OTH) AF: 0.00 AC: 0 AN: 56422

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000621 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		0.49
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs763593018; hg19: chr4-186064586;