6-31161690-G-T

Variant names:

• chr6-31161690-G-T
• rs779159917
• NM_007109.3:c.482G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007109.3(TCF19):​c.482G>T​(p.Arg161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R161Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16726857).

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.482G>T	p.Arg161Leu	missense	Exon 3 of 4	NP_009040.2	A0A1U9X8M7
	TCF19	NM_001077511.2		c.482G>T	p.Arg161Leu	missense	Exon 3 of 4	NP_001070979.1	A0A1U9X8M7
	TCF19	NM_001318908.2		c.482G>T	p.Arg161Leu	missense	Exon 4 of 5	NP_001305837.1	Q9Y242

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.482G>T	p.Arg161Leu	missense	Exon 3 of 4	ENSP00000365433.3	Q9Y242
	TCF19	ENST00000376255.4	TSL:1	c.482G>T	p.Arg161Leu	missense	Exon 3 of 4	ENSP00000365431.4	Q9Y242
	TCF19	ENST00000706778.1		c.482G>T	p.Arg161Leu	missense	Exon 4 of 5	ENSP00000516543.1	Q9Y242

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0081	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.068
Sift	Benign	0.31	T
Sift4G	Benign	0.59	T
Polyphen		0.98	D
Vest4		0.17
MutPred		0.21		Loss of phosphorylation at S164 (P = 0.0747)
MVP		0.32
MPC		1.3
ClinPred		0.84	D
GERP RS		4.8
PromoterAI		-0.048	Neutral
Varity_R		0.14
gMVP		0.34
Mutation Taster		=92/8	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: rs779159917; hg19: chr6-31129467;