15-44961579-G-A

Variant names:

• chr15-44961579-G-A
• rs1431226548
• NM_152448.3:c.343G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152448.3(TERB2):​c.343G>A​(p.Glu115Lys) 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. 13/19 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: TERB2 NM_152448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.120

Genes affected

TERB2 (HGNC:28520): (telomere repeat binding bouquet formation protein 2) Predicted to be involved in homologous chromosome pairing at meiosis and meiotic attachment of telomere to nuclear envelope. Predicted to be located in chromosome, telomeric region. Predicted to be active in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056364745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERB2	NM_152448.3	c.343G>A	p.Glu115Lys	missense_variant	Exon 4 of 7	ENST00000340827.4	NP_689661.1
TERB2	XM_011521240.3	c.343G>A	p.Glu115Lys	missense_variant	Exon 4 of 5		XP_011519542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERB2	ENST00000340827.4	c.343G>A	p.Glu115Lys	missense_variant	Exon 4 of 7	1	NM_152448.3	ENSP00000340644.3
TERB2	ENST00000559137.5	n.*309G>A		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000454013.1
TERB2	ENST00000559137.5	n.*309G>A		3_prime_UTR_variant	Exon 3 of 6	5		ENSP00000454013.1
TERB2	ENST00000557864.1	n.*252+3067G>A		intron_variant	Intron 2 of 5	3		ENSP00000452951.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.343G>A (p.E115K) alteration is located in exon 4 (coding exon 4) of the TERB2 gene. This alteration results from a G to A substitution at nucleotide position 343, causing the glutamic acid (E) at amino acid position 115 to be replaced by a lysine (K). 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	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.015
Sift	Benign	0.095	T
Sift4G	Benign	0.48	T
Polyphen		0.0040	B
Vest4		0.14
MutPred		0.34		Gain of methylation at E115 (P = 0.0076);
MVP		0.081
MPC		0.53
ClinPred		0.062	T
GERP RS		0.31
Varity_R		0.11
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs1431226548; hg19: chr15-45253777;