6-31162798-C-G

Variant names:

• chr6-31162798-C-G
• rs9501503
• NM_007109.3:c.*81C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007109.3(TCF19):​c.*81C>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 0.0014 in 1,528,750 control chromosomes in the GnomAD database, including 24 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 0.0069 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (11 hom.)
• Consequence: TCF19 NM_007109.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 1 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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00688 (1047/152248) while in subpopulation AFR AF = 0.0238 (989/41536). AF 95% confidence interval is 0.0226. There are 13 homozygotes in GnomAd4. There are 478 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	NM_007109.3	MANE Select	c.*81C>G		3_prime_UTR	Exon 4 of 4	NP_009040.2
	TCF19	NM_001077511.2		c.*81C>G		3_prime_UTR	Exon 4 of 4	NP_001070979.1
	TCF19	NM_001318908.2		c.*81C>G		3_prime_UTR	Exon 5 of 5	NP_001305837.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.*81C>G		3_prime_UTR	Exon 4 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.*81C>G		3_prime_UTR	Exon 4 of 4	ENSP00000365431.4
	TCF19	ENST00000706778.1		c.*81C>G		3_prime_UTR	Exon 5 of 5	ENSP00000516543.1

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1047 AN: 152130 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000790 AC: 1088 AN: 1376502 Hom.: 11 Cov.: 68 AF XY: 0.000698 AC XY: 473 AN XY: 677776

African (AFR) AF: 0.0284 AC: 908 AN: 31918

American (AMR) AF: 0.00169 AC: 62 AN: 36624

Ashkenazi Jewish (ASJ) AF: 0.000137 AC: 3 AN: 21954

East Asian (EAS) AF: 0.00 AC: 0 AN: 38088

South Asian (SAS) AF: 0.0000535 AC: 4 AN: 74698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35374

Middle Eastern (MID) AF: 0.000230 AC: 1 AN: 4346

European-Non Finnish (NFE) AF: 0.0000307 AC: 33 AN: 1076120

Other (OTH) AF: 0.00134 AC: 77 AN: 57380

GnomAD4 genome AF: 0.00688 AC: 1047 AN: 152248 Hom.: 13 Cov.: 32 AF XY: 0.00642 AC XY: 478 AN XY: 74452

African (AFR) AF: 0.0238 AC: 989 AN: 41536

American (AMR) AF: 0.00294 AC: 45 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.000840 Hom.: 0

Bravo AF: 0.00825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.93
DANN	Benign	0.57
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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: rs9501503; hg19: chr6-31130575;