8-96258669-T-C

Position:

• chr8-96258669-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015942.5(MTERF3):​c.22A>G​(p.Ile8Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTERF3 NM_015942.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0420

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

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=0.07238558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF3	NM_015942.5	c.22A>G	p.Ile8Val	missense_variant	2/8	ENST00000287025.4	NP_057026.3
MTERF3	NM_001286643.1	c.22A>G	p.Ile8Val	missense_variant	2/9		NP_001273572.1
MTERF3	NM_001362964.1	c.-514A>G		5_prime_UTR_variant	2/8		NP_001349893.1
MTERF3	XM_011517054.3	c.-448A>G		5_prime_UTR_variant	2/8		XP_011515356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF3	ENST00000287025.4	c.22A>G	p.Ile8Val	missense_variant	2/8	1	NM_015942.5	ENSP00000287025	P1
MTERF3	ENST00000523821.5	c.22A>G	p.Ile8Val	missense_variant	2/9	1		ENSP00000429400
MTERF3	ENST00000517720.1	c.22A>G	p.Ile8Val	missense_variant	3/3	3		ENSP00000429526

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 16, 2023

The c.22A>G (p.I8V) alteration is located in exon 2 (coding exon 1) of the MTERF3 gene. This alteration results from a A to G substitution at nucleotide position 22, causing the isoleucine (I) at amino acid position 8 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.073	.;T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.45	T;T;.
Polyphen		0.0050	B;B;.
Vest4		0.27
MutPred		0.16		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.36
MPC		0.024
ClinPred		0.061	T
GERP RS		0.13
Varity_R		0.021
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: chr8-97270897;