rs749363533

Variant names:

• chr8-96250940-T-A
• rs749363533
• NM_015942.5:c.643A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-96250940-T-A
• chr8-96250940-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015942.5(MTERF3):​c.643A>T​(p.Ile215Phe) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I215V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MTERF3 NM_015942.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 publications found

Genes affected

MTERF3 (HGNC:24258): (mitochondrial transcription termination factor 3) Enables transcription cis-regulatory region binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015942.5. 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
	MTERF3	NM_015942.5	MANE Select	c.643A>T	p.Ile215Phe	missense	Exon 4 of 8	NP_057026.3
	MTERF3	NM_001286643.1		c.643A>T	p.Ile215Phe	missense	Exon 4 of 9	NP_001273572.1	E5RIK9
	MTERF3	NM_001362964.1		c.73A>T	p.Ile25Phe	missense	Exon 4 of 8	NP_001349893.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTERF3	ENST00000287025.4	TSL:1 MANE Select	c.643A>T	p.Ile215Phe	missense	Exon 4 of 8	ENSP00000287025.3	Q96E29-1
	MTERF3	ENST00000523821.5	TSL:1	c.643A>T	p.Ile215Phe	missense	Exon 4 of 9	ENSP00000429400.1	E5RIK9
	MTERF3	ENST00000903462.1		c.685A>T	p.Ile229Phe	missense	Exon 5 of 9	ENSP00000573521.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-1.2	T
PhyloP100		2.7
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.63		Loss of catalytic residue at L220 (P = 0.061)
MVP		0.38
MPC		0.24
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.74
gMVP		0.79
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs749363533; hg19: chr8-97263168;