chr6-31161930-C-T

Variant names:

• chr6-31161930-C-T
• rs2073724
• NM_007109.3:c.722C>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.722C>T​(p.Pro241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 1,612,854 control chromosomes in the GnomAD database, including 6,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.086 (672 hom., cov: 33)
  • Exomes 𝑓: 0.080 (5416 hom.)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684
• Publications: 50 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 (MetaRNN=0.0016442835).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 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.722C>T	p.Pro241Leu	missense	Exon 3 of 4	NP_009040.2
	TCF19	NM_001077511.2		c.722C>T	p.Pro241Leu	missense	Exon 3 of 4	NP_001070979.1
	TCF19	NM_001318908.2		c.722C>T	p.Pro241Leu	missense	Exon 4 of 5	NP_001305837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.722C>T	p.Pro241Leu	missense	Exon 3 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.722C>T	p.Pro241Leu	missense	Exon 3 of 4	ENSP00000365431.4
	TCF19	ENST00000706778.1		c.722C>T	p.Pro241Leu	missense	Exon 4 of 5	ENSP00000516543.1

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13129 AN: 152166 Hom.: 672 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.102 AC: 25001 AN: 244278 AF XY: 0.102

Gnomad AFR exome AF: 0.0563

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.0456

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.0945

GnomAD4 exome AF: 0.0797 AC: 116358 AN: 1460570 Hom.: 5416 Cov.: 35 AF XY: 0.0807 AC XY: 58621 AN XY: 726616

African (AFR) AF: 0.0543 AC: 1816 AN: 33474

American (AMR) AF: 0.156 AC: 6992 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3586 AN: 26136

East Asian (EAS) AF: 0.0460 AC: 1825 AN: 39698

South Asian (SAS) AF: 0.0991 AC: 8548 AN: 86248

European-Finnish (FIN) AF: 0.163 AC: 8523 AN: 52216

Middle Eastern (MID) AF: 0.116 AC: 670 AN: 5764

European-Non Finnish (NFE) AF: 0.0713 AC: 79308 AN: 1111948

Other (OTH) AF: 0.0843 AC: 5090 AN: 60380

GnomAD4 genome AF: 0.0863 AC: 13141 AN: 152284 Hom.: 672 Cov.: 33 AF XY: 0.0906 AC XY: 6743 AN XY: 74446

African (AFR) AF: 0.0550 AC: 2287 AN: 41560

American (AMR) AF: 0.118 AC: 1804 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.0430 AC: 223 AN: 5186

South Asian (SAS) AF: 0.0941 AC: 454 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1905 AN: 10600

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0818 AC: 5565 AN: 68020

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.0846 Hom.: 2693

Bravo AF: 0.0822

TwinsUK AF: 0.0626 AC: 232

ALSPAC AF: 0.0672 AC: 259

ESP6500AA AF: 0.0533 AC: 135

ESP6500EA AF: 0.0856 AC: 437

ExAC AF: 0.0980 AC: 11441

Asia WGS AF: 0.0780 AC: 272 AN: 3478

EpiCase AF: 0.0958

EpiControl AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.68
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.043
Sift	Benign	0.34	T
Sift4G	Benign	0.098	T
Polyphen		0.91	P
Vest4		0.10
MPC		0.58
ClinPred		0.0079	T
GERP RS		3.6
PromoterAI		-0.016	Neutral
Varity_R		0.023
gMVP		0.20
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: rs2073724; hg19: chr6-31129707; COSMIC: COSV52563633; COSMIC: COSV52563633;