chr6-31161865-A-G

Position:

• chr6-31161865-A-G

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>G​(p.Pro219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,612,900 control chromosomes in the GnomAD database, including 1,967 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 0.044 (174 hom., cov: 35)
  • Exomes 𝑓: 0.044 (1793 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=-0.85).
• BP7: Synonymous conserved (PhyloP=0.321 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6653 AN: 152168 Hom.: 174 Cov.: 35

Gnomad AFR AF: 0.0343

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0474

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0416

GnomAD3 exomes AF: 0.0494 AC: 12050 AN: 243768 Hom.: 379 AF XY: 0.0526 AC XY: 7019 AN XY: 133438

Gnomad AFR exome AF: 0.0359

Gnomad AMR exome AF: 0.0285

Gnomad ASJ exome AF: 0.0842

Gnomad EAS exome AF: 0.0188

Gnomad SAS exome AF: 0.0873

Gnomad FIN exome AF: 0.0547

Gnomad NFE exome AF: 0.0476

Gnomad OTH exome AF: 0.0583

GnomAD4 exome AF: 0.0435 AC: 63600 AN: 1460614 Hom.: 1793 Cov.: 84 AF XY: 0.0458 AC XY: 33243 AN XY: 726620

Gnomad4 AFR exome AF: 0.0319

Gnomad4 AMR exome AF: 0.0303

Gnomad4 ASJ exome AF: 0.0822

Gnomad4 EAS exome AF: 0.0754

Gnomad4 SAS exome AF: 0.0852

Gnomad4 FIN exome AF: 0.0564

Gnomad4 NFE exome AF: 0.0384

Gnomad4 OTH exome AF: 0.0440

GnomAD4 genome AF: 0.0438 AC: 6665 AN: 152286 Hom.: 174 Cov.: 35 AF XY: 0.0446 AC XY: 3318 AN XY: 74454

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.0475

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.00889 Hom.: 33816

EpiCase AF: 0.0430

EpiControl AF: 0.0443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.51

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;