6-31161863-C-T

Position:

• chr6-31161863-C-T

Variant summary

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

The NM_007109.3(TCF19):​c.655C>T​(p.Pro219Ser) 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.

• Frequency: Genomes: not found (cov: 35)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.257

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]

TCF19 (HGNC:):

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=0.05095917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF19	NM_007109.3	c.655C>T	p.Pro219Ser	missense_variant	3/4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8	c.655C>T	p.Pro219Ser	missense_variant	3/4	1	NM_007109.3	ENSP00000365433.3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 35

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.655C>T (p.P219S) alteration is located in exon 3 (coding exon 2) of the TCF19 gene. This alteration results from a C to T substitution at nucleotide position 655, causing the proline (P) at amino acid position 219 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.72
DEOGEN2	Benign	0.0014	T;T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.76	.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.051	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.21	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.19	B;B;.
Vest4		0.15
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);.;
MVP		0.099
MPC		1.3
ClinPred		0.089	T
GERP RS		0.43
Varity_R		0.025
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31129640;