chr9-37888010-A-G

Position:

• chr9-37888010-A-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.541T>C​(p.Phe181Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 4.21

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 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=0.1184333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A51	NM_033412.4	c.541T>C	p.Phe181Leu	missense_variant	3/3	ENST00000242275.7
SLC25A51	NR_024872.3	n.210-6379T>C		intron_variant, non_coding_transcript_variant
SLC25A51	NR_024873.3	n.183-6379T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A51	ENST00000242275.7	c.541T>C	p.Phe181Leu	missense_variant	3/3	2	NM_033412.4	P1
SLC25A51	ENST00000496760.5	n.409-6379T>C		intron_variant, non_coding_transcript_variant		1
SLC25A51	ENST00000377716.6	c.541T>C	p.Phe181Leu	missense_variant	3/3	3		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Oct 29, 2021

The c.541T>C (p.F181L) 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 541, causing the phenylalanine (F) at amino acid position 181 to be replaced by a leucine (L). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.082	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.50	N;N
MutationTaster	Benign	0.70	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.12
Sift	Benign	0.97	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.043
MutPred		0.25		Loss of methylation at R182 (P = 0.1059);Loss of methylation at R182 (P = 0.1059);
MVP		0.29
MPC		1.1
ClinPred		0.49	T
GERP RS		3.5
Varity_R		0.045
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-37888007;