chr8-96257072-G-A

Variant names:

• chr8-96257072-G-A
• NM_015942.5:c.377C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015942.5(MTERF3):​c.377C>T​(p.Ser126Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTERF3 NM_015942.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.377C>T	p.Ser126Leu	missense	Exon 3 of 8	NP_057026.3
	MTERF3	NM_001286643.1		c.377C>T	p.Ser126Leu	missense	Exon 3 of 9	NP_001273572.1	E5RIK9
	MTERF3	NM_001362964.1		c.-194C>T		5_prime_UTR	Exon 3 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.377C>T	p.Ser126Leu	missense	Exon 3 of 8	ENSP00000287025.3	Q96E29-1
	MTERF3	ENST00000523821.5	TSL:1	c.377C>T	p.Ser126Leu	missense	Exon 3 of 9	ENSP00000429400.1	E5RIK9
	MTERF3	ENST00000903462.1		c.419C>T	p.Ser140Leu	missense	Exon 4 of 9	ENSP00000573521.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.89	T
PhyloP100		4.7
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.94	P
Vest4		0.52
MutPred		0.55		Loss of phosphorylation at S126 (P = 0.0256)
MVP		0.67
MPC		0.15
ClinPred		0.92	D
GERP RS		6.2
PromoterAI		-0.018	Neutral
Varity_R		0.12
gMVP		0.51
Mutation Taster		=81/19	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

hg19: chr8-97269300; COSMIC: COSV54634811; COSMIC: COSV54634811;