dbSNP rs3213491: SLC25A1:c.442-118T>G (chr22-19177322-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.883

Publications

4 publications found

Variant links:

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 links:

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

LINC01311 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC25A1	NM_005984.5 link	c.442-118T>G	intron_variant	Intron 4 of 8	ENST00000215882.10	NP_005975.1	P53007
SLC25A1	NM_001256534.2 link	c.463-118T>G	intron_variant	Intron 3 of 7		NP_001243463.1	D9HTE9
SLC25A1	NM_001287387.2 link	c.133-118T>G	intron_variant	Intron 4 of 8		NP_001274316.1	D3DX16
SLC25A1	NR_046298.3 link	n.366-118T>G	intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A1	ENST00000215882.10 link	c.442-118T>G		intron_variant	Intron 4 of 8	1	NM_005984.5	ENSP00000215882.5		P53007

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21230

AN:

151848

Hom.:

2550

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2374

4747

7121

9494

11868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.140

AC:

21259

AN:

151966

Hom.:

2551

Cov.:

AF XY:

0.141

AC XY:

10509

AN XY:

74270

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0478

AC:

3246

AN:

67948

Other (OTH)

AF:

0.123

AC:

260

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

797

1594

2390

3187

3984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

228

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.6

(source)

DANN

Benign

0.68

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over