6-31162725-T-C

Variant names:

• chr6-31162725-T-C
• rs1065461
• NM_007109.3:c.*8T>C

Variant summary

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

The NM_007109.3(TCF19):​c.*8T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,608,936 control chromosomes in the GnomAD database, including 455,942 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 0.78 (46515 hom., cov: 31)
  • Exomes 𝑓: 0.75 (409427 hom.)
• Consequence: TCF19 NM_007109.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 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.*8T>C		3_prime_UTR	Exon 4 of 4	NP_009040.2
	TCF19	NR_199382.1		n.1538T>C		non_coding_transcript_exon	Exon 5 of 5
	TCF19	NM_001077511.2		c.*8T>C		3_prime_UTR	Exon 4 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.*8T>C		3_prime_UTR	Exon 4 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.*8T>C		3_prime_UTR	Exon 4 of 4	ENSP00000365431.4
	TCF19	ENST00000496421.1	TSL:3	n.598T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118525 AN: 151914 Hom.: 46476 Cov.: 31

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: 0.747

Gnomad OTH AF: 0.817

GnomAD2 exomes AF: 0.752 AC: 181083 AN: 240728 AF XY: 0.752

Gnomad AFR exome AF: 0.846

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.699

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.748 AC: 1090442 AN: 1456904 Hom.: 409427 Cov.: 92 AF XY: 0.747 AC XY: 541862 AN XY: 724940

African (AFR) AF: 0.851 AC: 28493 AN: 33470

American (AMR) AF: 0.770 AC: 34394 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 22365 AN: 26070

East Asian (EAS) AF: 0.647 AC: 25690 AN: 39686

South Asian (SAS) AF: 0.712 AC: 61411 AN: 86206

European-Finnish (FIN) AF: 0.741 AC: 36274 AN: 48982

Middle Eastern (MID) AF: 0.832 AC: 4790 AN: 5760

European-Non Finnish (NFE) AF: 0.747 AC: 830908 AN: 1111726

Other (OTH) AF: 0.764 AC: 46117 AN: 60338

GnomAD4 genome AF: 0.780 AC: 118618 AN: 152032 Hom.: 46515 Cov.: 31 AF XY: 0.779 AC XY: 57886 AN XY: 74312

African (AFR) AF: 0.847 AC: 35095 AN: 41444

American (AMR) AF: 0.804 AC: 12286 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2992 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3504 AN: 5168

South Asian (SAS) AF: 0.687 AC: 3303 AN: 4808

European-Finnish (FIN) AF: 0.749 AC: 7938 AN: 10592

Middle Eastern (MID) AF: 0.884 AC: 258 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50786 AN: 67956

Other (OTH) AF: 0.816 AC: 1721 AN: 2110

Alfa AF: 0.764 Hom.: 100467

Bravo AF: 0.790

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.43
PhyloP100		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1065461; hg19: chr6-31130502; COSMIC: COSV52564592; COSMIC: COSV52564592;