rs2073722

Positions:

• chr6-31161865-A-C
• chr6-31161865-A-G
• chr6-31161865-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007109.3(TCF19):​c.657A>C​(p.Pro219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,612,642 control chromosomes in the GnomAD database, including 457,288 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 0.78 (46629 hom., cov: 35)
  • Exomes 𝑓: 0.75 (410659 hom.)
• Consequence: TCF19 NM_007109.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=0.321 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF19	NM_007109.3	c.657A>C	p.Pro219=	synonymous_variant	3/4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8	c.657A>C	p.Pro219=	synonymous_variant	3/4	1	NM_007109.3	ENSP00000365433	P1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118767 AN: 152148 Hom.: 46590 Cov.: 35

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.817

GnomAD3 exomes AF: 0.752 AC: 183292 AN: 243768 Hom.: 69388 AF XY: 0.752 AC XY: 100279 AN XY: 133438

Gnomad AFR exome AF: 0.847

Gnomad AMR exome AF: 0.760

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.698

Gnomad SAS exome AF: 0.703

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.749 AC: 1093328 AN: 1460376 Hom.: 410659 Cov.: 84 AF XY: 0.748 AC XY: 543146 AN XY: 726502

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.770

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.748

Gnomad4 OTH exome AF: 0.764

GnomAD4 genome AF: 0.781 AC: 118860 AN: 152266 Hom.: 46629 Cov.: 35 AF XY: 0.779 AC XY: 58030 AN XY: 74446

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.816

Alfa AF: 0.801 Hom.: 33816

EpiCase AF: 0.768

EpiControl AF: 0.781

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.9
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs2073722; hg19: chr6-31129642; COSMIC: COSV52562926; COSMIC: COSV52562926;