rs2073721

Variant names:

• chr6-31161839-A-C
• rs2073721
• NM_007109.3:c.631A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31161839-A-C
• chr6-31161839-A-G

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.631A>C​(p.Met211Leu) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M211V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 59 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=0.03649351).

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.631A>C	p.Met211Leu	missense	Exon 3 of 4	NP_009040.2
	TCF19	NM_001077511.2		c.631A>C	p.Met211Leu	missense	Exon 3 of 4	NP_001070979.1
	TCF19	NM_001318908.2		c.631A>C	p.Met211Leu	missense	Exon 4 of 5	NP_001305837.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF19	ENST00000376257.8	TSL:1 MANE Select	c.631A>C	p.Met211Leu	missense	Exon 3 of 4	ENSP00000365433.3
	TCF19	ENST00000376255.4	TSL:1	c.631A>C	p.Met211Leu	missense	Exon 3 of 4	ENSP00000365431.4
	TCF19	ENST00000706778.1		c.631A>C	p.Met211Leu	missense	Exon 4 of 5	ENSP00000516543.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.7
DANN	Benign	0.48
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.059
Sift	Benign	0.37	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.13		Gain of phosphorylation at T213 (P = 0.0941)
MVP		0.030
MPC		0.46
ClinPred		0.029	T
GERP RS		4.5
PromoterAI		0.011	Neutral
Varity_R		0.057
gMVP		0.082
Mutation Taster		=99/1	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: rs2073721; hg19: chr6-31129616;