rs2073721

chr6-31161839-A-Cchr6-31161839-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007109.3(TCF19):c.631A>C(p.Met211Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M211V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03649351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3	c.631A>C	p.Met211Leu	missense_variant	3/4	ENST00000376257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF19	ENST00000376257.8	c.631A>C	p.Met211Leu	missense_variant	3/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.7
Dann	Benign	0.48
DEOGEN2	Benign	0.0011	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.047	N
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.15	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.046
MutPred		0.13		Gain of phosphorylation at T213 (P = 0.0941);Gain of phosphorylation at T213 (P = 0.0941);.;
MVP		0.030
MPC		0.46
ClinPred		0.029	T
GERP RS		4.5
Varity_R		0.057
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2073721; hg19: chr6-31129616;