5-141303324-A-T

Variant names:

• chr5-141303324-A-T
• rs3749779
• NM_031947.4:c.542T>A
• SLC25A2 p.Val181Glu

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031947.4(SLC25A2):​c.542T>A​(p.Val181Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SLC25A2 NM_031947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77
• Publications: 0 publications found

Genes affected

SLC25A2 (HGNC:22921): (solute carrier family 25 member 2) This intronless gene encodes a protein that localizes to the mitochondrial inner membrane and likely functions as a transporter of small molecules such as ornithine. This gene is located between the protocadherin beta and gamma gene clusters on chromosome 5. [provided by RefSeq, Dec 2014]

TAF7 (HGNC:11541): (TATA-box binding protein associated factor 7) The intronless gene for this transcription coactivator is located between the protocadherin beta and gamma gene clusters on chromosome 5. The protein encoded by this gene is a component of the TFIID protein complex, a complex which binds to the TATA box in class II promoters and recruits RNA polymerase II and other factors. This particular subunit interacts with the largest TFIID subunit, as well as multiple transcription activators. The protein is required for transcription by promoters targeted by RNA polymerase II. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031947.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A2	NM_031947.4	MANE Select	c.542T>A	p.Val181Glu	missense	Exon 1 of 1	NP_114153.1	Q9BXI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A2	ENST00000239451.7	TSL:6 MANE Select	c.542T>A	p.Val181Glu	missense	Exon 1 of 1	ENSP00000239451.4	Q9BXI2
	TAF7	ENST00000624699.1	TSL:3	n.128+17194T>A		intron	N/A
	TAF7	ENST00000686518.1		n.75+17194T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		7.8
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.2	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Varity_R		0.90
gMVP		0.45
Mutation Taster		=90/10	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3749779;

hg19: chr5-140682891;