rs3216869

Variant names:

• chr6-31162466-ACTTC-A
• rs3216869
• NM_007109.3:c.798-6_798-3delCTTC

Your query was ambiguous. Multiple possible variants found:

• chr6-31162466-ACTTC-A
• chr6-31162466-ACTTC-ACTTCCTTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_007109.3(TCF19):​c.798-6_798-3delCTTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 1,600,416 control chromosomes in the GnomAD database, including 2,141 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (498 hom., cov: 31)
  • Exomes 𝑓: 0.034 (1643 hom.)
• Consequence: TCF19 NM_007109.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007109.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	NM_007109.3	MANE Select	c.798-6_798-3delCTTC		splice_region intron	N/A	NP_009040.2
	TCF19	NM_001077511.2		c.798-6_798-3delCTTC		splice_region intron	N/A	NP_001070979.1
	TCF19	NM_001318908.2		c.798-6_798-3delCTTC		splice_region intron	N/A	NP_001305837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.798-10_798-7delCTTC		splice_region intron	N/A	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.798-10_798-7delCTTC		splice_region intron	N/A	ENSP00000365431.4
	TCF19	ENST00000706778.1		c.798-10_798-7delCTTC		splice_region intron	N/A	ENSP00000516543.1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9661 AN: 151858 Hom.: 496 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0638

GnomAD2 exomes AF: 0.0476 AC: 11047 AN: 232124 AF XY: 0.0454

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.0321

Gnomad EAS exome AF: 0.176

Gnomad FIN exome AF: 0.0555

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0416

GnomAD4 exome AF: 0.0335 AC: 48569 AN: 1448440 Hom.: 1643 AF XY: 0.0332 AC XY: 23850 AN XY: 719414

African (AFR) AF: 0.138 AC: 4591 AN: 33250

American (AMR) AF: 0.0245 AC: 1074 AN: 43854

Ashkenazi Jewish (ASJ) AF: 0.0287 AC: 717 AN: 24986

East Asian (EAS) AF: 0.184 AC: 7285 AN: 39634

South Asian (SAS) AF: 0.0360 AC: 3025 AN: 84060

European-Finnish (FIN) AF: 0.0577 AC: 2987 AN: 51740

Middle Eastern (MID) AF: 0.0320 AC: 182 AN: 5684

European-Non Finnish (NFE) AF: 0.0234 AC: 25920 AN: 1105360

Other (OTH) AF: 0.0466 AC: 2788 AN: 59872

GnomAD4 genome AF: 0.0636 AC: 9665 AN: 151976 Hom.: 498 Cov.: 31 AF XY: 0.0647 AC XY: 4803 AN XY: 74278

African (AFR) AF: 0.136 AC: 5643 AN: 41414

American (AMR) AF: 0.0343 AC: 524 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3468

East Asian (EAS) AF: 0.165 AC: 852 AN: 5152

South Asian (SAS) AF: 0.0413 AC: 198 AN: 4790

European-Finnish (FIN) AF: 0.0525 AC: 555 AN: 10572

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1639 AN: 67976

Other (OTH) AF: 0.0645 AC: 136 AN: 2108

Alfa AF: 0.0405 Hom.: 42

Bravo AF: 0.0671

Asia WGS AF: 0.113 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3216869; hg19: chr6-31130243;