16-66767452-A-T

Variant names:

• chr16-66767452-A-T
• rs1181037767
• NM_001136505.2:c.1743T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001136505.2(TERB1):​c.1743T>A​(p.Thr581Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T581T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TERB1 NM_001136505.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 0 publications found

Genes affected

TERB1 (HGNC:26675): (telomere repeat binding bouquet formation protein 1) 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 and nuclear inner membrane. Predicted to colocalize with shelterin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=0.235 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136505.2. 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
	TERB1	NM_001136505.2	MANE Select	c.1743T>A	p.Thr581Thr	synonymous	Exon 16 of 19	NP_001129977.1	Q8NA31-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERB1	ENST00000433154.6	TSL:5 MANE Select	c.1743T>A	p.Thr581Thr	synonymous	Exon 16 of 19	ENSP00000463762.1	Q8NA31-1
	TERB1	ENST00000558713.6	TSL:5	c.1743T>A	p.Thr581Thr	synonymous	Exon 15 of 18	ENSP00000462883.1	Q8NA31-1
	TERB1	ENST00000313294.7	TSL:5	n.*25T>A		non_coding_transcript_exon	Exon 14 of 16	ENSP00000464579.1	Q8NA31-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		0.23

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: rs1181037767; hg19: chr16-66801355;