6-31162497-G-C

Variant names:

• chr6-31162497-G-C
• rs371901587
• NM_007109.3:c.818G>C

Variant summary

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

The NM_007109.3(TCF19):​c.818G>C​(p.Arg273Pro) 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. 12/21 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: not found (cov: 32)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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=0.066964716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF19	NM_007109.3	c.818G>C	p.Arg273Pro	missense_variant	Exon 4 of 4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8	c.818G>C	p.Arg273Pro	missense_variant	Exon 4 of 4	1	NM_007109.3	ENSP00000365433.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.058	T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.037
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.0	B;B
Vest4		0.10
MutPred		0.27		Loss of MoRF binding (P = 0.0064);Loss of MoRF binding (P = 0.0064);
MVP		0.25
MPC		1.6
ClinPred		0.98	D
GERP RS		0.43
Varity_R		0.52
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs371901587; hg19: chr6-31130274;