6-31164308-T-C

Variant names:

• chr6-31164308-T-C
• rs3130933
• ENST00000706788.1:n.2580T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000706788.1(TCF19):​n.2580T>C 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 0.879 in 1,290,672 control chromosomes in the GnomAD database, including 500,464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.92 (64223 hom., cov: 31)
  • Exomes 𝑓: 0.87 (436241 hom.)
• Consequence: TCF19 ENST00000706788.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 32 publications found

Genes affected

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.*293A>G		downstream_gene_variant		ENST00000259915.13	NP_002692.2
TCF19	NM_007109.3	c.*1591T>C		downstream_gene_variant		ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.*293A>G		downstream_gene_variant		1	NM_002701.6	ENSP00000259915.7
TCF19	ENST00000376257.8	c.*1591T>C		downstream_gene_variant		1	NM_007109.3	ENSP00000365433.3

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139494 AN: 152112 Hom.: 64160 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.969

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.942

GnomAD4 exome AF: 0.874 AC: 995267 AN: 1138442 Hom.: 436241 Cov.: 16 AF XY: 0.877 AC XY: 484173 AN XY: 551956

African (AFR) AF: 0.981 AC: 24787 AN: 25278

American (AMR) AF: 0.949 AC: 16392 AN: 17266

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 16437 AN: 16822

East Asian (EAS) AF: 0.965 AC: 27806 AN: 28810

South Asian (SAS) AF: 0.965 AC: 55517 AN: 57520

European-Finnish (FIN) AF: 0.878 AC: 30947 AN: 35252

Middle Eastern (MID) AF: 0.971 AC: 3076 AN: 3168

European-Non Finnish (NFE) AF: 0.858 AC: 778449 AN: 907438

Other (OTH) AF: 0.893 AC: 41856 AN: 46888

GnomAD4 genome AF: 0.917 AC: 139615 AN: 152230 Hom.: 64223 Cov.: 31 AF XY: 0.920 AC XY: 68485 AN XY: 74438

African (AFR) AF: 0.976 AC: 40558 AN: 41538

American (AMR) AF: 0.942 AC: 14413 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3391 AN: 3472

East Asian (EAS) AF: 0.983 AC: 5083 AN: 5172

South Asian (SAS) AF: 0.969 AC: 4677 AN: 4828

European-Finnish (FIN) AF: 0.888 AC: 9407 AN: 10594

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58954 AN: 68010

Other (OTH) AF: 0.943 AC: 1992 AN: 2112

Alfa AF: 0.887 Hom.: 214927

Bravo AF: 0.925

Asia WGS AF: 0.968 AC: 3366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.88
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3130933; hg19: chr6-31132085;