rs2073722

Variant names:

• chr6-31161865-A-C
• rs2073722
• NM_007109.3:c.657A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001438635.1(TCF19):​c.488A>C​(p.His163Pro) variant causes a missense 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. 5/6 in silico tools predict 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_001438635.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438635.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	NM_007109.3	MANE Select	c.657A>C	p.Pro219Pro	synonymous	Exon 3 of 4	NP_009040.2
	TCF19	NM_001438635.1		c.488A>C	p.His163Pro	missense	Exon 5 of 6	NP_001425564.1
	TCF19	NM_001438636.1		c.488A>C	p.His163Pro	missense	Exon 4 of 5	NP_001425565.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.657A>C	p.Pro219Pro	synonymous	Exon 3 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.657A>C	p.Pro219Pro	synonymous	Exon 3 of 4	ENSP00000365431.4
	TCF19	ENST00000706783.1		c.488A>C	p.His163Pro	missense	Exon 4 of 5	ENSP00000516548.1

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

GnomAD2 exomes AF: 0.752 AC: 183292 AN: 243768 AF XY: 0.752

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 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

African (AFR) AF: 0.851 AC: 28498 AN: 33472

American (AMR) AF: 0.770 AC: 34388 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 22415 AN: 26132

East Asian (EAS) AF: 0.647 AC: 25689 AN: 39688

South Asian (SAS) AF: 0.712 AC: 61426 AN: 86228

European-Finnish (FIN) AF: 0.741 AC: 38690 AN: 52216

Middle Eastern (MID) AF: 0.832 AC: 4793 AN: 5764

European-Non Finnish (NFE) AF: 0.748 AC: 831280 AN: 1111842

Other (OTH) AF: 0.764 AC: 46149 AN: 60374

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

African (AFR) AF: 0.847 AC: 35224 AN: 41570

American (AMR) AF: 0.805 AC: 12313 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2990 AN: 3468

East Asian (EAS) AF: 0.678 AC: 3505 AN: 5172

South Asian (SAS) AF: 0.687 AC: 3318 AN: 4830

European-Finnish (FIN) AF: 0.749 AC: 7950 AN: 10612

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50839 AN: 67994

Other (OTH) AF: 0.816 AC: 1726 AN: 2114

Alfa AF: 0.801 Hom.: 50149

EpiCase AF: 0.768

EpiControl AF: 0.781

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.9
DANN	Benign	0.52
PhyloP100		0.32
PromoterAI		0.14	Neutral
Mutation Taster		=100/0	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: rs2073722; hg19: chr6-31129642; COSMIC: COSV52562926; COSMIC: COSV52562926;