NM_005984.5:c.442-118T>G

Variant names:

• chr22-19177322-A-C
• rs3213491
• NM_005984.5:c.442-118T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

LINC01311 (HGNC:50503): (long intergenic non-protein coding RNA 1311)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005984.5. 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
	SLC25A1	NM_005984.5	MANE Select	c.442-118T>G		intron	N/A	NP_005975.1	P53007
	SLC25A1	NM_001256534.2		c.463-118T>G		intron	N/A	NP_001243463.1	D9HTE9
	SLC25A1	NM_001287387.2		c.133-118T>G		intron	N/A	NP_001274316.1	D3DX16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A1	ENST00000215882.10	TSL:1 MANE Select	c.442-118T>G		intron	N/A	ENSP00000215882.5	P53007
	SLC25A1	ENST00000880508.1		c.481-118T>G		intron	N/A	ENSP00000550567.1
	SLC25A1	ENST00000880513.1		c.451-118T>G		intron	N/A	ENSP00000550572.1

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

African (AFR) AF: 0.283 AC: 4835 AN: 17114

American (AMR) AF: 0.159 AC: 4217 AN: 26468

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1677 AN: 16622

East Asian (EAS) AF: 0.471 AC: 15159 AN: 32218

South Asian (SAS) AF: 0.103 AC: 5749 AN: 55870

European-Finnish (FIN) AF: 0.0619 AC: 2766 AN: 44652

Middle Eastern (MID) AF: 0.0770 AC: 296 AN: 3846

European-Non Finnish (NFE) AF: 0.0449 AC: 20123 AN: 448406

Other (OTH) AF: 0.0976 AC: 3270 AN: 33514

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

African (AFR) AF: 0.289 AC: 11982 AN: 41430

American (AMR) AF: 0.129 AC: 1975 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 339 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2174 AN: 5112

South Asian (SAS) AF: 0.114 AC: 547 AN: 4816

European-Finnish (FIN) AF: 0.0599 AC: 634 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0478 AC: 3246 AN: 67948

Other (OTH) AF: 0.123 AC: 260 AN: 2110

Alfa AF: 0.111 Hom.: 228

Bravo AF: 0.155

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs3213491; hg19: chr22-19164835;