16-66778897-C-G

Variant names:

• chr16-66778897-C-G
• rs1032721059
• NM_001136505.2:c.819G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001136505.2(TERB1):​c.819G>C​(p.Val273Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,372,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TERB1 NM_001136505.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0950
• 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=-0.43).
• BP6: Variant 16-66778897-C-G is Benign according to our data. Variant chr16-66778897-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3388875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.095 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.819G>C	p.Val273Val	synonymous	Exon 10 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.819G>C	p.Val273Val	synonymous	Exon 10 of 19	ENSP00000463762.1	Q8NA31-1
	TERB1	ENST00000558713.6	TSL:5	c.819G>C	p.Val273Val	synonymous	Exon 9 of 18	ENSP00000462883.1	Q8NA31-1
	TERB1	ENST00000673664.1		c.786G>C	p.Val262Val	synonymous	Exon 10 of 12	ENSP00000500999.1	A0A669KAY0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000644 AC: 1 AN: 155248 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000429

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000364 AC: 5 AN: 1372486 Hom.: 0 Cov.: 31 AF XY: 0.00000595 AC XY: 4 AN XY: 672112

African (AFR) AF: 0.00 AC: 0 AN: 31126

American (AMR) AF: 0.0000870 AC: 3 AN: 34470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24748

East Asian (EAS) AF: 0.00 AC: 0 AN: 35006

South Asian (SAS) AF: 0.00 AC: 0 AN: 76942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058536

Other (OTH) AF: 0.0000352 AC: 2 AN: 56886

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.8
DANN	Benign	0.68
PhyloP100		0.095

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: rs1032721059; hg19: chr16-66812800;