6-31161488-C-G

Variant names:

• chr6-31161488-C-G
• rs201756282
• NM_007109.3:c.280C>G

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.280C>G​(p.Leu94Val) 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. 14/22 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. L94M) 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: 0.745
• Publications: 0 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=0.096307606).

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.280C>G	p.Leu94Val	missense	Exon 3 of 4	NP_009040.2	A0A1U9X8M7
	TCF19	NM_001077511.2		c.280C>G	p.Leu94Val	missense	Exon 3 of 4	NP_001070979.1	A0A1U9X8M7
	TCF19	NM_001318908.2		c.280C>G	p.Leu94Val	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.280C>G	p.Leu94Val	missense	Exon 3 of 4	ENSP00000365433.3	Q9Y242
	TCF19	ENST00000376255.4	TSL:1	c.280C>G	p.Leu94Val	missense	Exon 3 of 4	ENSP00000365431.4	Q9Y242
	TCF19	ENST00000706778.1		c.280C>G	p.Leu94Val	missense	Exon 4 of 5	ENSP00000516543.1	Q9Y242

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.74	N
PhyloP100		0.74
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.13
Sift	Benign	0.39	T
Sift4G	Benign	0.26	T
Polyphen		0.57	P
Vest4		0.16
MutPred		0.34		Loss of phosphorylation at S97 (P = 0.1658)
MVP		0.65
MPC		1.3
ClinPred		0.53	D
GERP RS		3.8
PromoterAI		0.014	Neutral
Varity_R		0.10
gMVP		0.24
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs201756282; hg19: chr6-31129265;