chr6-31161516-C-A

Variant names:

• chr6-31161516-C-A
• rs899519362
• NM_007109.3:c.308C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007109.3(TCF19):​c.308C>A​(p.Thr103Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,547,942 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.308C>A	p.Thr103Asn	missense	Exon 3 of 4	NP_009040.2	A0A1U9X8M7
	TCF19	NM_001077511.2		c.308C>A	p.Thr103Asn	missense	Exon 3 of 4	NP_001070979.1	A0A1U9X8M7
	TCF19	NM_001318908.2		c.308C>A	p.Thr103Asn	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.308C>A	p.Thr103Asn	missense	Exon 3 of 4	ENSP00000365433.3	Q9Y242
	TCF19	ENST00000376255.4	TSL:1	c.308C>A	p.Thr103Asn	missense	Exon 3 of 4	ENSP00000365431.4	Q9Y242
	TCF19	ENST00000706778.1		c.308C>A	p.Thr103Asn	missense	Exon 4 of 5	ENSP00000516543.1	Q9Y242

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1395692 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690628

African (AFR) AF: 0.0000326 AC: 1 AN: 30696

American (AMR) AF: 0.00 AC: 0 AN: 32332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21994

East Asian (EAS) AF: 0.00 AC: 0 AN: 38246

South Asian (SAS) AF: 0.00 AC: 0 AN: 74488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084446

Other (OTH) AF: 0.0000174 AC: 1 AN: 57512

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74386

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.41		Loss of glycosylation at T103 (P = 0.0123)
MVP		0.93
MPC		1.5
ClinPred		0.94	D
GERP RS		5.7
PromoterAI		-0.044	Neutral
Varity_R		0.31
gMVP		0.63
Mutation Taster		=86/14	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: rs899519362; hg19: chr6-31129293;