NM_007109.3:c.-303C>T

Variant names:

• chr6-31159167-C-T
• rs3094187
• NM_007109.3:c.-303C>T

Variant summary

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

The NM_007109.3(TCF19):​c.-303C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 403,756 control chromosomes in the GnomAD database, including 56,317 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (22928 hom., cov: 32)
  • Exomes 𝑓: 0.51 (33389 hom.)
• Consequence: TCF19 NM_007109.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• Publications: 34 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 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.-303C>T		5_prime_UTR	Exon 2 of 4	NP_009040.2
	TCF19	NR_199382.1		n.405C>T		non_coding_transcript_exon	Exon 2 of 5
	TCF19	NM_001077511.2		c.-303C>T		5_prime_UTR	Exon 2 of 4	NP_001070979.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.-303C>T		5_prime_UTR	Exon 2 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.-303C>T		5_prime_UTR	Exon 2 of 4	ENSP00000365431.4
	TCF19	ENST00000706784.1		n.456C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82785 AN: 151908 Hom.: 22924 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.534

GnomAD4 exome AF: 0.508 AC: 127959 AN: 251730 Hom.: 33389 Cov.: 0 AF XY: 0.507 AC XY: 65476 AN XY: 129122

African (AFR) AF: 0.631 AC: 4724 AN: 7482

American (AMR) AF: 0.518 AC: 4663 AN: 8994

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 5668 AN: 9196

East Asian (EAS) AF: 0.552 AC: 11032 AN: 19996

South Asian (SAS) AF: 0.494 AC: 6247 AN: 12636

European-Finnish (FIN) AF: 0.451 AC: 8007 AN: 17746

Middle Eastern (MID) AF: 0.524 AC: 670 AN: 1278

European-Non Finnish (NFE) AF: 0.495 AC: 78303 AN: 158126

Other (OTH) AF: 0.531 AC: 8645 AN: 16276

GnomAD4 genome AF: 0.545 AC: 82819 AN: 152026 Hom.: 22928 Cov.: 32 AF XY: 0.542 AC XY: 40235 AN XY: 74286

African (AFR) AF: 0.632 AC: 26195 AN: 41450

American (AMR) AF: 0.545 AC: 8330 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2203 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2893 AN: 5154

South Asian (SAS) AF: 0.500 AC: 2408 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4783 AN: 10552

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34256 AN: 67990

Other (OTH) AF: 0.535 AC: 1127 AN: 2108

Alfa AF: 0.523 Hom.: 58327

Bravo AF: 0.557

Asia WGS AF: 0.564 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.82
PhyloP100		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs3094187; hg19: chr6-31126944; COSMIC: COSV66161127; COSMIC: COSV66161127;