rs7750641

Variant names:

• chr6-31161533-C-T
• rs7750641
• NM_007109.3:c.325C>T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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
• Publications: 70 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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TCF19	NM_007109.3	c.325C>T	p.Pro109Ser	missense_variant	Exon 3 of 4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8	c.325C>T	p.Pro109Ser	missense_variant	Exon 3 of 4	1	NM_007109.3	ENSP00000365433.3

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

GnomAD2 exomes AF: 0.0701 AC: 14472 AN: 206418 AF XY: 0.0689

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 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

African (AFR) AF: 0.0264 AC: 828 AN: 31398

American (AMR) AF: 0.0303 AC: 1090 AN: 35946

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 1136 AN: 23556

East Asian (EAS) AF: 0.000104 AC: 4 AN: 38450

South Asian (SAS) AF: 0.000381 AC: 30 AN: 78656

European-Finnish (FIN) AF: 0.0778 AC: 3987 AN: 51270

Middle Eastern (MID) AF: 0.00736 AC: 41 AN: 5574

European-Non Finnish (NFE) AF: 0.142 AC: 155782 AN: 1093352

Other (OTH) AF: 0.105 AC: 6118 AN: 58434

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

African (AFR) AF: 0.0275 AC: 1143 AN: 41556

American (AMR) AF: 0.0374 AC: 572 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0744 AC: 790 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8358 AN: 67998

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.106 Hom.: 4726

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

Apr 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
LIST_S2	Benign	0.51	.;T;T
MetaRNN	Benign	0.0012	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M;.
PhyloP100		-0.18
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
PromoterAI		-0.026	Neutral
Varity_R		0.045
gMVP		0.17
Mutation Taster		=99/1	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: rs7750641; hg19: chr6-31129310;