NM_007109.3:c.818G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 13/22 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. R273Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066964716).

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.818G>C	p.Arg273Pro	missense	Exon 4 of 4	NP_009040.2	A0A1U9X8M7
	TCF19	NM_001077511.2		c.818G>C	p.Arg273Pro	missense	Exon 4 of 4	NP_001070979.1	A0A1U9X8M7
	TCF19	NM_001318908.2		c.818G>C	p.Arg273Pro	missense	Exon 5 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.818G>C	p.Arg273Pro	missense	Exon 4 of 4	ENSP00000365433.3	Q9Y242
	TCF19	ENST00000376255.4	TSL:1	c.818G>C	p.Arg273Pro	missense	Exon 4 of 4	ENSP00000365431.4	Q9Y242
	TCF19	ENST00000706778.1		c.818G>C	p.Arg273Pro	missense	Exon 5 of 5	ENSP00000516543.1	Q9Y242

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.37
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.037
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.014	D
Polyphen		0.0	B
Vest4		0.10
MutPred		0.27		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
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs371901587; hg19: chr6-31130274;