chr6-167373273-G-A

Variant names:

• chr6-167373273-G-A
• rs200948850
• ENST00000397829.9:n.1063C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The ENST00000397829.9(TCP10L3):​n.1063C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 150,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 41)
  • Exomes 𝑓: 0.00045 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCP10L3 ENST00000397829.9 non_coding_transcript_exon
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0440
• Publications: 1 publications found

Genes affected

TCP10L3 (HGNC:):

TCP10L3 (HGNC:11656): (t-complex 10 like 3 (pseudogene))

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: BayesDel_addAF computational evidence supports a deleterious effect, 0.262

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397829.9. 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
	TCP10L3	NR_163193.1		n.943C>T		non_coding_transcript_exon	Exon 6 of 6
	TCP10L3	NR_163194.1		n.1089C>T		non_coding_transcript_exon	Exon 8 of 8
	TCP10L3	NR_163195.1		n.1016C>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP10L3	ENST00000397829.9	TSL:1	n.1063C>T		non_coding_transcript_exon	Exon 8 of 8
	TCP10L3	ENST00000514083.1	TSL:1	n.1539C>T		non_coding_transcript_exon	Exon 2 of 2
	TCP10L3	ENST00000463894.7	TSL:2	n.3324C>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.00340 AC: 513 AN: 150698 Hom.: 0 Cov.: 41

Gnomad AFR AF: 0.00418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00278

Gnomad ASJ AF: 0.00321

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00227

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.00674

GnomAD2 exomes AF: 0.000440 AC: 109 AN: 247698 AF XY: 0.000432

Gnomad AFR exome AF: 0.00505

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000499

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000449 AC: 651 AN: 1450478 Hom.: 1 Cov.: 42 AF XY: 0.000461 AC XY: 333 AN XY: 721610

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00500 AC: 167 AN: 33420

American (AMR) AF: 0.000338 AC: 15 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.000618 AC: 16 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86102

European-Finnish (FIN) AF: 0.000453 AC: 24 AN: 52938

Middle Eastern (MID) AF: 0.000703 AC: 4 AN: 5686

European-Non Finnish (NFE) AF: 0.000336 AC: 370 AN: 1102408

Other (OTH) AF: 0.000818 AC: 49 AN: 59888

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00340 AC: 513 AN: 150816 Hom.: 0 Cov.: 41 AF XY: 0.00350 AC XY: 258 AN XY: 73806

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00415 AC: 172 AN: 41470

American (AMR) AF: 0.00277 AC: 42 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00321 AC: 11 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00227 AC: 24 AN: 10556

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00366 AC: 245 AN: 66900

Other (OTH) AF: 0.00667 AC: 14 AN: 2100

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00360 Hom.: 0

ESP6500AA AF: 0.00347 AC: 13

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00222 AC: 268

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	7.7
DANN	Benign	0.93
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.051	N
PhyloP100		0.044
Vest4		0.049
GERP RS		0.93
Mutation Taster		=199/1	polymorphism

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: rs200948850; hg19: chr6-167786761; COSMIC: COSV64752377; COSMIC: COSV64752377;