4-185143447-G-C

Position:

• chr4-185143447-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The ENST00000281456.11(SLC25A4):​c.75G>C​(p.Ala25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,357,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A25A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SLC25A4 ENST00000281456.11 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.403

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 4-185143447-G-C is Benign according to our data. Variant chr4-185143447-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2962251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.403 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000125 (17/1357086) while in subpopulation SAS AF= 0.000146 (11/75390). AF 95% confidence interval is 0.000081. There are 0 homozygotes in gnomad4_exome. There are 13 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A4	NM_001151.4	c.75G>C	p.Ala25=	synonymous_variant	1/4	ENST00000281456.11	NP_001142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A4	ENST00000281456.11	c.75G>C	p.Ala25=	synonymous_variant	1/4	1	NM_001151.4	ENSP00000281456	P1
SLC25A4	ENST00000491736.1	c.75G>C	p.Ala25=	synonymous_variant, NMD_transcript_variant	1/4	5		ENSP00000476711

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000551 AC: 7 AN: 127044 Hom.: 0 AF XY: 0.0000736 AC XY: 5 AN XY: 67960

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000481

Gnomad ASJ exome AF: 0.000258

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000203

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000125 AC: 17 AN: 1357086 Hom.: 0 Cov.: 29 AF XY: 0.0000194 AC XY: 13 AN XY: 669460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000313

Gnomad4 ASJ exome AF: 0.000126

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.46e-7

Gnomad4 OTH exome AF: 0.0000179

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 05, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.80
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

Publications

LitVar

Other links and lift over

dbSNP: rs778584154; hg19: chr4-186064601;