6-31161533-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007109.3(TCF19):c.325C>T(p.Pro109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,568,924 control chromosomes in the GnomAD database, including 13,139 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.074 (624 hom., cov: 33)
  • Exomes 𝑓: 0.12 (12515 hom.)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012408197).
• BP6: Variant 6-31161533-C-T is Benign according to our data. Variant chr6-31161533-C-T is described in ClinVar as [Benign]. Clinvar id is 1280459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3	c.325C>T	p.Pro109Ser	missense_variant	3/4	ENST00000376257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF19	ENST00000376257.8	c.325C>T	p.Pro109Ser	missense_variant	3/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11285 AN: 152170 Hom.: 624 Cov.: 33

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0556

GnomAD3 exomes AF: 0.0701 AC: 14472 AN: 206418 Hom.: 879 AF XY: 0.0689 AC XY: 7787 AN XY: 113074

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.0283

Gnomad ASJ exome AF: 0.0465

Gnomad EAS exome AF: 0.0000649

Gnomad SAS exome AF: 0.000260

Gnomad FIN exome AF: 0.0750

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.0731

GnomAD4 exome AF: 0.119 AC: 169016 AN: 1416636 Hom.: 12515 Cov.: 31 AF XY: 0.115 AC XY: 81102 AN XY: 702858

Gnomad4 AFR exome AF: 0.0264

Gnomad4 AMR exome AF: 0.0303

Gnomad4 ASJ exome AF: 0.0482

Gnomad4 EAS exome AF: 0.000104

Gnomad4 SAS exome AF: 0.000381

Gnomad4 FIN exome AF: 0.0778

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0741 AC: 11286 AN: 152288 Hom.: 624 Cov.: 33 AF XY: 0.0684 AC XY: 5090 AN XY: 74466

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.106 Hom.: 2040

Bravo AF: 0.0699

TwinsUK AF: 0.157 AC: 581

ALSPAC AF: 0.154 AC: 593

ESP6500AA AF: 0.0291 AC: 67

ESP6500EA AF: 0.118 AC: 592

ExAC AF: 0.0659 AC: 7652

Asia WGS AF: 0.00636 AC: 23 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 30, 2020

This variant is associated with the following publications: (PMID: 20662065, 23055271) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	11
Dann	Benign	0.94
DEOGEN2	Benign	0.0021	T;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.037	N
MetaRNN	Benign	0.0012	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.10	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.039
MPC		0.54
ClinPred		0.0036	T
GERP RS		-1.2
Varity_R		0.045
gMVP		0.17

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: rs7750641; hg19: chr6-31129310;