rs2073724

Variant names:

• chr6-31161930-C-G
• rs2073724
• NM_007109.3:c.722C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31161930-C-G
• chr6-31161930-C-T

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.722C>G​(p.Pro241Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684
• Publications: 50 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=0.13121378).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	NM_007109.3	MANE Select	c.722C>G	p.Pro241Arg	missense	Exon 3 of 4	NP_009040.2
	TCF19	NM_001077511.2		c.722C>G	p.Pro241Arg	missense	Exon 3 of 4	NP_001070979.1
	TCF19	NM_001318908.2		c.722C>G	p.Pro241Arg	missense	Exon 4 of 5	NP_001305837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.722C>G	p.Pro241Arg	missense	Exon 3 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.722C>G	p.Pro241Arg	missense	Exon 3 of 4	ENSP00000365431.4
	TCF19	ENST00000706778.1		c.722C>G	p.Pro241Arg	missense	Exon 4 of 5	ENSP00000516543.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460640 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 726648

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.00069	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.68
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.043
Sift	Benign	0.27	T
Sift4G	Benign	0.20	T
Polyphen		0.91	P
Vest4		0.15
MutPred		0.18		Loss of catalytic residue at P240 (P = 0.0179)
MVP		0.22
MPC		0.64
ClinPred		0.30	T
GERP RS		3.6
PromoterAI		-0.030	Neutral
Varity_R		0.023
gMVP		0.19
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs2073724; hg19: chr6-31129707;