9-37888226-G-A

Position:

• chr9-37888226-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_033412.4(SLC25A51):​c.325C>T​(p.Leu109Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A51 NM_033412.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

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]

ENSG00000255872 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A51	NM_033412.4	c.325C>T	p.Leu109Phe	missense_variant	3/3	ENST00000242275.7	NP_219480.1
PAICSP1		n.37888226G>A		intragenic_variant
SLC25A51	NR_024872.3	n.210-6595C>T		intron_variant
SLC25A51	NR_024873.3	n.183-6595C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A51	ENST00000242275.7	c.325C>T	p.Leu109Phe	missense_variant	3/3	2	NM_033412.4	ENSP00000242275.6
SLC25A51	ENST00000496760.5	n.409-6595C>T		intron_variant		1
ENSG00000255872	ENST00000540557.1	n.*681+11603C>T		intron_variant		5		ENSP00000457548.1
SLC25A51	ENST00000377716.6	c.325C>T	p.Leu109Phe	missense_variant	3/3	3		ENSP00000366945.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2023

The c.325C>T (p.L109F) alteration is located in exon 3 (coding exon 1) of the SLC25A51 gene. This alteration results from a C to T substitution at nucleotide position 325, causing the leucine (L) at amino acid position 109 to be replaced by a phenylalanine (F). 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	Benign	0.19
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	.;D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.030	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.56
Sift	Benign	0.039	D;D
Sift4G	Uncertain	0.039	D;D
Polyphen		0.97	D;D
Vest4		0.62
MutPred		0.67		Loss of stability (P = 0.0592);Loss of stability (P = 0.0592);
MVP		0.76
MPC		1.8
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-37888223;