22-19177322-A-C

Position:

• chr22-19177322-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005984.5(SLC25A1):​c.442-118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 830,676 control chromosomes in the GnomAD database, including 8,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2551 hom., cov: 33)
  • Exomes 𝑓: 0.086 (5968 hom.)
• Consequence: SLC25A1 NM_005984.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.883

Genes affected

SLC25A1 (HGNC:10979): (solute carrier family 25 member 1) This gene encodes a member of the mitochondrial carrier subfamily of solute carrier proteins. Members of this family include nuclear-encoded transporters that translocate small metabolites across the mitochondrial membrane. This protein regulates the movement of citrate across the inner membranes of the mitochondria. Mutations in this gene have been associated with combined D-2- and L-2-hydroxyglutaric aciduria. Pseudogenes of this gene have been identified on chromosomes 7, 11, 16, and 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

SLC25A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-19177322-A-C is Benign according to our data. Variant chr22-19177322-A-C is described in ClinVar as [Benign]. Clinvar id is 1253224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A1	NM_005984.5	c.442-118T>G		intron_variant		ENST00000215882.10	NP_005975.1
SLC25A1	NM_001256534.2	c.463-118T>G		intron_variant			NP_001243463.1
SLC25A1	NM_001287387.2	c.133-118T>G		intron_variant			NP_001274316.1
SLC25A1	NR_046298.3	n.366-118T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A1	ENST00000215882.10	c.442-118T>G		intron_variant		1	NM_005984.5	ENSP00000215882.5
SLC25A1	ENST00000451283.5	c.133-118T>G		intron_variant		2		ENSP00000401480.1
SLC25A1	ENST00000461267.1	n.588-118T>G		intron_variant		3
SLC25A1	ENST00000470922.5	n.584-118T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21230 AN: 151848 Hom.: 2550 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0856 AC: 58092 AN: 678710 Hom.: 5968 AF XY: 0.0856 AC XY: 29953 AN XY: 350018

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0619

Gnomad4 NFE exome AF: 0.0449

Gnomad4 OTH exome AF: 0.0976

GnomAD4 genome AF: 0.140 AC: 21259 AN: 151966 Hom.: 2551 Cov.: 33 AF XY: 0.141 AC XY: 10509 AN XY: 74270

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0978

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0599

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.123

Alfa AF: 0.103 Hom.: 191

Bravo AF: 0.155

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.68

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: rs3213491; hg19: chr22-19164835;