6-31161865-A-G

Variant names:

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

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>G​(p.His163Arg) variant causes a missense 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. 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 0.044 (174 hom., cov: 35)
  • Exomes 𝑓: 0.044 (1793 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0887 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>G	p.Pro219Pro	synonymous	Exon 3 of 4	NP_009040.2
	TCF19	NM_001438635.1		c.488A>G	p.His163Arg	missense	Exon 5 of 6	NP_001425564.1
	TCF19	NM_001438636.1		c.488A>G	p.His163Arg	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>G	p.Pro219Pro	synonymous	Exon 3 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.657A>G	p.Pro219Pro	synonymous	Exon 3 of 4	ENSP00000365431.4
	TCF19	ENST00000706783.1		c.488A>G	p.His163Arg	missense	Exon 4 of 5	ENSP00000516548.1

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

GnomAD2 exomes AF: 0.0494 AC: 12050 AN: 243768 AF XY: 0.0526

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 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

African (AFR) AF: 0.0319 AC: 1069 AN: 33480

American (AMR) AF: 0.0303 AC: 1353 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0822 AC: 2149 AN: 26134

East Asian (EAS) AF: 0.0754 AC: 2995 AN: 39696

South Asian (SAS) AF: 0.0852 AC: 7346 AN: 86254

European-Finnish (FIN) AF: 0.0564 AC: 2947 AN: 52270

Middle Eastern (MID) AF: 0.0621 AC: 358 AN: 5764

European-Non Finnish (NFE) AF: 0.0384 AC: 42726 AN: 1111944

Other (OTH) AF: 0.0440 AC: 2657 AN: 60376

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

African (AFR) AF: 0.0344 AC: 1431 AN: 41574

American (AMR) AF: 0.0321 AC: 491 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3470

East Asian (EAS) AF: 0.0475 AC: 246 AN: 5174

South Asian (SAS) AF: 0.0959 AC: 463 AN: 4830

European-Finnish (FIN) AF: 0.0539 AC: 572 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0450 AC: 3061 AN: 67996

Other (OTH) AF: 0.0412 AC: 87 AN: 2114

Alfa AF: 0.00598 Hom.: 50149

EpiCase AF: 0.0430

EpiControl AF: 0.0443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.51
PhyloP100		0.32
PromoterAI		-0.021	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;