9-37888472-T-C

Position:

• chr9-37888472-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033412.4(SLC25A51):​c.79A>G​(p.Asn27Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: SLC25A51 NM_033412.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.556

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048962533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A51	NM_033412.4	c.79A>G	p.Asn27Asp	missense_variant	3/3	ENST00000242275.7
SLC25A51	NR_024872.3	n.210-6841A>G		intron_variant, non_coding_transcript_variant
SLC25A51	NR_024873.3	n.183-6841A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A51	ENST00000242275.7	c.79A>G	p.Asn27Asp	missense_variant	3/3	2	NM_033412.4	P1
SLC25A51	ENST00000496760.5	n.409-6841A>G		intron_variant, non_coding_transcript_variant		1
SLC25A51	ENST00000377716.6	c.79A>G	p.Asn27Asp	missense_variant	3/3	3		P1

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

Jan 30, 2024

The c.79A>G (p.N27D) 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 79, causing the asparagine (N) at amino acid position 27 to be replaced by an aspartic acid (D). 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	0.065
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.4
DANN	Benign	0.95
DEOGEN2	Benign	0.042	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.29	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.14
Sift	Benign	0.33	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0010	B;B
Vest4		0.080
MutPred		0.36		Gain of ubiquitination at K32 (P = 0.1103);Gain of ubiquitination at K32 (P = 0.1103);
MVP		0.20
MPC		1.1
ClinPred		0.054	T
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1831511057; hg19: chr9-37888469;