Menu
GeneBe

8-132867060-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_003235.5(TG):c.60T>C(p.Asn20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,598,432 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

TG
NM_003235.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.928
Variant links:
Genes affected
TG (HGNC:11764): (thyroglobulin) Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thryroid gland. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to its site of iodination, and subsequent thyroxine biosynthesis, in the follicular lumen. Mutations in this gene cause thyroid dyshormonogenesis, manifested as goiter, and are associated with moderate to severe congenital hypothyroidism. Polymorphisms in this gene are associated with susceptibility to autoimmune thyroid diseases (AITD) such as Graves disease and Hashimoto thryoiditis. [provided by RefSeq, Nov 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-132867060-T-C is Benign according to our data. Variant chr8-132867060-T-C is described in ClinVar as [Benign]. Clinvar id is 726990.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.928 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TGNM_003235.5 linkuse as main transcriptc.60T>C p.Asn20= synonymous_variant 1/48 ENST00000220616.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGENST00000220616.9 linkuse as main transcriptc.60T>C p.Asn20= synonymous_variant 1/481 NM_003235.5 P1P01266-1
TGENST00000523901.1 linkuse as main transcriptc.60T>C p.Asn20= synonymous_variant, NMD_transcript_variant 1/65

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000263
AC:
40
AN:
152136
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000357
AC:
80
AN:
223996
Hom.:
0
AF XY:
0.000440
AC XY:
53
AN XY:
120556
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000459
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000694
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000427
Gnomad OTH exome
AF:
0.000704
GnomAD4 exome
AF:
0.000256
AC:
370
AN:
1446178
Hom.:
0
Cov.:
31
AF XY:
0.000287
AC XY:
206
AN XY:
717738
show subpopulations
Gnomad4 AFR exome
AF:
0.0000904
Gnomad4 AMR exome
AF:
0.000346
Gnomad4 ASJ exome
AF:
0.0000388
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000622
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000244
Gnomad4 OTH exome
AF:
0.000268
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000263
AC:
40
AN:
152254
Hom.:
1
Cov.:
31
AF XY:
0.000282
AC XY:
21
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000397
Hom.:
1
Bravo
AF:
0.000253

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
6.6
Dann
Benign
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140030312; hg19: chr8-133879305; COSMIC: COSV55083340; API