Genetic Variant NM_005888.4:c.645-90C>T (chr12-98599865-C-T) – 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_005888.4(SLC25A3):c.645-90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,368,960 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 51 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 41 hom. )

Consequence

SLC25A3
NM_005888.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.646

Publications

2 publications found

Variant links:

Genes affected

SLC25A3 (HGNC:10989): (solute carrier family 25 member 3) The protein encoded by this gene catalyzes the transport of phosphate into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions. The protein contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier family. Both the N-terminal and C-terminal regions of this protein protrude toward the cytosol. Multiple alternatively spliced transcript variants have been isolated. [provided by RefSeq, Jul 2008]

SLC25A3 links:

SNORA53 (HGNC:32646): (small nucleolar RNA, H/ACA box 53)

SNORA53 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=-0.85).

BP6

Variant 12-98599865-C-T is Benign according to our data. Variant chr12-98599865-C-T is described in ClinVar as Benign. ClinVar VariationId is 1228798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005888.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A3	NM_005888.4	MANE Plus Clinical	c.645-90C>T	intron	N/A	NP_005879.1	Q00325-1
SLC25A3	NM_002635.4	MANE Select	c.642-90C>T	intron	N/A	NP_002626.1	A0A024RBE8
SLC25A3	NM_213611.3		c.642-90C>T	intron	N/A	NP_998776.1	Q00325-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC25A3	ENST00000228318.8	TSL:5 MANE Plus Clinical	c.645-90C>T	intron	N/A	ENSP00000228318.3	Q00325-1
SLC25A3	ENST00000552981.6	TSL:1 MANE Select	c.642-90C>T	intron	N/A	ENSP00000448708.2	Q00325-2
SLC25A3	ENST00000188376.9	TSL:1	c.642-90C>T	intron	N/A	ENSP00000188376.5	Q00325-2

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2351

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00958

GnomAD2 exomes

AF:

0.00406

AC:

1015

AN:

250080

AF XY:

0.00304

show subpopulations

Gnomad AFR exome

AF:

0.0564

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00158

AC:

1925

AN:

1216746

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

867

AN XY:

617598

show subpopulations

African (AFR)

AF:

0.0551

AC:

1583

AN:

28710

American (AMR)

AF:

0.00254

AC:

113

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24562

East Asian (EAS)

AF:

0.00

AC:

AN:

38604

South Asian (SAS)

AF:

0.000235

AC:

AN:

80892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51826

Middle Eastern (MID)

AF:

0.00149

AC:

AN:

5370

European-Non Finnish (NFE)

AF:

0.0000595

AC:

AN:

890104

Other (OTH)

AF:

0.00285

AC:

149

AN:

52258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

109

217

326

434

543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0155

AC:

2352

AN:

152214

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1095

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0543

AC:

2255

AN:

41514

American (AMR)

AF:

0.00438

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68006

Other (OTH)

AF:

0.00948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00495

Hom.:

Bravo

AF:

0.0176

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.57

(source)

DANN

Benign

0.84

PhyloP100

-0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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

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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