chr22-19178640-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_005984.5(SLC25A1):c.34G>A(p.Ala12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000497 in 1,185,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

SLC25A1
NM_005984.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.584

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2557655).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000597 (9/150708) while in subpopulation SAS AF = 0.00186 (9/4828). AF 95% confidence interval is 0.000972. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A1	NM_005984.5	MANE Select	c.34G>A	p.Ala12Thr	missense	Exon 1 of 9	NP_005975.1	P53007
SLC25A1	NR_046298.3		n.97G>A		non_coding_transcript_exon	Exon 1 of 8
SLC25A1	NM_001256534.2		c.-285G>A		upstream_gene	N/A	NP_001243463.1	D9HTE9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A1	ENST00000215882.10	TSL:1 MANE Select	c.34G>A	p.Ala12Thr	missense	Exon 1 of 9	ENSP00000215882.5	P53007
SLC25A1	ENST00000880508.1		c.34G>A	p.Ala12Thr	missense	Exon 1 of 9	ENSP00000550567.1
SLC25A1	ENST00000880513.1		c.34G>A	p.Ala12Thr	missense	Exon 1 of 9	ENSP00000550572.1

Frequencies

GnomAD3 genomes

AF:

0.0000597

AC:

AN:

150708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000483

AC:

AN:

1035248

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

488234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21132

American (AMR)

AF:

0.00

AC:

AN:

6908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12190

East Asian (EAS)

AF:

0.00

AC:

AN:

22406

South Asian (SAS)

AF:

0.00209

AC:

AN:

19120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19266

Middle Eastern (MID)

AF:

0.000373

AC:

AN:

2678

European-Non Finnish (NFE)

AF:

0.00000561

AC:

AN:

891278

Other (OTH)

AF:

0.0000993

AC:

AN:

40270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000597

AC:

AN:

150708

Hom.:

Cov.:

AF XY:

0.0000816

AC XY:

AN XY:

73570

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41274

American (AMR)

AF:

0.00

AC:

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00186

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67488

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000936

Hom.:

Bravo

AF:

0.0000189

Asia WGS

AF:

0.00206

AC:

AN:

3406

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.0083

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.7

PhyloP100

0.58

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Benign

0.23

Sift4G

Uncertain

0.033

Polyphen

0.059

Vest4

0.20

MutPred

0.27

Gain of glycosylation at A12 (P = 4e-04)

MVP

0.72

MPC

1.8

ClinPred

0.55

GERP RS

2.3

PromoterAI

-0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Varity_R

0.11

gMVP

0.59

Mutation Taster

=66/34

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over