6-31162983-A-G

Variant names:

• chr6-31162983-A-G
• rs1841
• NM_007109.3:c.*266A>G

Variant summary

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

The NM_007109.3(TCF19):​c.*266A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 1,362,556 control chromosomes in the GnomAD database, including 3,930 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 0.065 (351 hom., cov: 33)
  • Exomes 𝑓: 0.072 (3579 hom.)
• Consequence: TCF19 NM_007109.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 13 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 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.*266A>G		3_prime_UTR	Exon 4 of 4	NP_009040.2
	TCF19	NR_199382.1		n.1796A>G		non_coding_transcript_exon	Exon 5 of 5
	TCF19	NM_001077511.2		c.*266A>G		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.*266A>G		3_prime_UTR	Exon 4 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.*266A>G		3_prime_UTR	Exon 4 of 4	ENSP00000365431.4
	TCF19	ENST00000496421.1	TSL:3	n.856A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9916 AN: 152166 Hom.: 354 Cov.: 33

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0618

GnomAD4 exome AF: 0.0720 AC: 87150 AN: 1210272 Hom.: 3579 Cov.: 59 AF XY: 0.0735 AC XY: 42681 AN XY: 581066

African (AFR) AF: 0.0377 AC: 1024 AN: 27172

American (AMR) AF: 0.0923 AC: 1292 AN: 13996

Ashkenazi Jewish (ASJ) AF: 0.0497 AC: 863 AN: 17370

East Asian (EAS) AF: 0.0354 AC: 1110 AN: 31384

South Asian (SAS) AF: 0.134 AC: 6424 AN: 48024

European-Finnish (FIN) AF: 0.0920 AC: 2360 AN: 25662

Middle Eastern (MID) AF: 0.124 AC: 418 AN: 3358

European-Non Finnish (NFE) AF: 0.0706 AC: 70127 AN: 993372

Other (OTH) AF: 0.0707 AC: 3532 AN: 49934

GnomAD4 genome AF: 0.0651 AC: 9910 AN: 152284 Hom.: 351 Cov.: 33 AF XY: 0.0666 AC XY: 4960 AN XY: 74464

African (AFR) AF: 0.0374 AC: 1556 AN: 41572

American (AMR) AF: 0.0806 AC: 1234 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 188 AN: 3472

East Asian (EAS) AF: 0.0397 AC: 206 AN: 5186

South Asian (SAS) AF: 0.123 AC: 592 AN: 4816

European-Finnish (FIN) AF: 0.0954 AC: 1012 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0724 AC: 4924 AN: 68014

Other (OTH) AF: 0.0616 AC: 130 AN: 2110

Alfa AF: 0.0721 Hom.: 645

Bravo AF: 0.0632

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.81
PhyloP100		-0.24
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: rs1841; hg19: chr6-31130760;