ENST00000397829.8:n.668G>A

Variant names:

• chr6-167376622-C-T
• rs201005141
• ENST00000397829.9:n.686G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000397829.9(TCP10L3):​n.686G>A 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 0.0401 in 829,432 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (5 hom., cov: 8)
  • Exomes 𝑓: 0.040 (189 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCP10L3 ENST00000397829.9 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0490
• Publications: 0 publications found

Genes affected

TCP10L3 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004687518).
• BP6: Variant 6-167376622-C-T is Benign according to our data. Variant chr6-167376622-C-T is described in ClinVar as Benign. ClinVar VariationId is 768122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

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.566G>A		non_coding_transcript_exon	Exon 3 of 6
	TCP10L3	NR_163194.1		n.712G>A		non_coding_transcript_exon	Exon 5 of 8
	TCP10L3	NR_163195.1		n.639G>A		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP10L3	ENST00000397829.9	TSL:1	n.686G>A		non_coding_transcript_exon	Exon 5 of 8
	TCP10L3	ENST00000460930.2	TSL:1	n.488G>A		non_coding_transcript_exon	Exon 3 of 3
	TCP10L3	ENST00000366827.6	TSL:5	n.712G>A		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 1075 AN: 65752 Hom.: 5 Cov.: 8

Gnomad AFR AF: 0.00662

Gnomad AMI AF: 0.00811

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.00721

Gnomad MID AF: 0.0313

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0188

GnomAD2 exomes AF: 0.0297 AC: 4063 AN: 136628 AF XY: 0.0292

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.0366

Gnomad ASJ exome AF: 0.0267

Gnomad EAS exome AF: 0.0581

Gnomad FIN exome AF: 0.00433

Gnomad NFE exome AF: 0.0272

Gnomad OTH exome AF: 0.0427

GnomAD4 exome AF: 0.0401 AC: 33270 AN: 829432 Hom.: 189 Cov.: 22 AF XY: 0.0429 AC XY: 17831 AN XY: 415268

African (AFR) AF: 0.0150 AC: 335 AN: 22312

American (AMR) AF: 0.0522 AC: 1138 AN: 21810

Ashkenazi Jewish (ASJ) AF: 0.0647 AC: 955 AN: 14758

East Asian (EAS) AF: 0.0641 AC: 1588 AN: 24770

South Asian (SAS) AF: 0.101 AC: 5205 AN: 51340

European-Finnish (FIN) AF: 0.0451 AC: 1422 AN: 31520

Middle Eastern (MID) AF: 0.0425 AC: 139 AN: 3274

European-Non Finnish (NFE) AF: 0.0333 AC: 20757 AN: 624186

Other (OTH) AF: 0.0488 AC: 1731 AN: 35462

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0163 AC: 1075 AN: 65812 Hom.: 5 Cov.: 8 AF XY: 0.0143 AC XY: 451 AN XY: 31498

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

African (AFR) AF: 0.00665 AC: 130 AN: 19556

American (AMR) AF: 0.0165 AC: 94 AN: 5694

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 26 AN: 1328

East Asian (EAS) AF: 0.0250 AC: 62 AN: 2484

South Asian (SAS) AF: 0.0397 AC: 52 AN: 1310

European-Finnish (FIN) AF: 0.00721 AC: 30 AN: 4160

Middle Eastern (MID) AF: 0.0259 AC: 3 AN: 116

European-Non Finnish (NFE) AF: 0.0220 AC: 659 AN: 29940

Other (OTH) AF: 0.0187 AC: 16 AN: 854

⚠️ 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: 0.0991 Hom.: 35

ExAC AF: 0.00156 AC: 103

ClinVar

ClinVar submissions

Significance: 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
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.4
DANN	Benign	0.91
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.049
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.060
Sift	Benign	0.48	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.043
MPC		2.1
ClinPred		0.0012	T
GERP RS		-3.8
gMVP		0.059
Mutation Taster		=100/0	polymorphism (auto)

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: rs201005141; hg19: chr6-167790110; COSMIC: COSV64749377; COSMIC: COSV64749377;