9-37888423-T-C

Variant names:

• chr9-37888423-T-C
• rs1831510429
• NM_033412.4:c.128A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033412.4(SLC25A51):​c.128A>G​(p.Asn43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLC25A51 NM_033412.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16292033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A51	NM_033412.4	c.128A>G	p.Asn43Ser	missense_variant	Exon 3 of 3	ENST00000242275.7	NP_219480.1
PAICSP1		n.37888423T>C		intragenic_variant
SLC25A51	NR_024872.3	n.210-6792A>G		intron_variant	Intron 3 of 4
SLC25A51	NR_024873.3	n.183-6792A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A51	ENST00000242275.7	c.128A>G	p.Asn43Ser	missense_variant	Exon 3 of 3	2	NM_033412.4	ENSP00000242275.6
SLC25A51	ENST00000496760.5	n.409-6792A>G		intron_variant	Intron 2 of 3	1
ENSG00000255872	ENST00000540557.1	n.*681+11406A>G		intron_variant	Intron 7 of 11	5		ENSP00000457548.1
SLC25A51	ENST00000377716.6	c.128A>G	p.Asn43Ser	missense_variant	Exon 3 of 3	3		ENSP00000366945.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727242

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.128A>G (p.N43S) alteration is located in exon 3 (coding exon 1) of the SLC25A51 gene. This alteration results from a A to G substitution at nucleotide position 128, causing the asparagine (N) at amino acid position 43 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	Benign	0.043
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.077	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.87	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.50	N;N
REVEL	Benign	0.11
Sift	Benign	0.65	T;T
Sift4G	Benign	0.085	T;T
Polyphen		0.0	B;B
Vest4		0.092
MutPred		0.41		Gain of glycosylation at N43 (P = 0.1061);Gain of glycosylation at N43 (P = 0.1061);
MVP		0.47
MPC		0.78
ClinPred		0.085	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.021
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1831510429; hg19: chr9-37888420;