Variant 9-37888288-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_033412.4(SLC25A51):c.263T>C(p.Leu88Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC25A51
NM_033412.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.82

Variant links:

Genes affected

SLC25A51 (HGNC:23323): (solute carrier family 25 member 51) Enables NAD transmembrane transporter activity. Involved in mitochondrial NAD transmembrane transport. Located in mitochondrion. Is active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A51 links:

ENSG00000255872 (HGNC:):

ENSG00000255872 links:

PAICSP1 (HGNC:8588): (phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase pseudogene 1)

PAICSP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A51	NM_033412.4 link	c.263T>C	p.Leu88Ser	missense_variant	3/3	ENST00000242275.7	NP_219480.1	Q9H1U9
PAICSP1		n.37888288A>G		intragenic_variant
SLC25A51	NR_024872.3 link	n.210-6657T>C		intron_variant
SLC25A51	NR_024873.3 link	n.183-6657T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC25A51	ENST00000242275.7 link	c.263T>C	p.Leu88Ser	missense_variant	3/3	2	NM_033412.4	ENSP00000242275.6	Q9H1U9
SLC25A51	ENST00000496760.5 link	n.409-6657T>C		intron_variant		1
ENSG00000255872	ENST00000540557.1 link	n.*681+11541T>C		intron_variant		5		ENSP00000457548.1
SLC25A51	ENST00000377716.6 link	c.263T>C	p.Leu88Ser	missense_variant	3/3	3		ENSP00000366945.2	Q9H1U9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152194

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.263T>C (p.L88S) alteration is located in exon 3 (coding exon 1) of the SLC25A51 gene. This alteration results from a T to C substitution at nucleotide position 263, causing the leucine (L) at amino acid position 88 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

.;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Uncertain

0.16

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.6

D;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.96

MutPred

0.77

Gain of disorder (P = 0.013);Gain of disorder (P = 0.013);

MVP

0.74

MPC

2.5

ClinPred

0.98

GERP RS

4.9

Varity_R

0.62

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over