6-31161839-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007109.3(TCF19):​c.631A>G​(p.Met211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,611,980 control chromosomes in the GnomAD database, including 457,232 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (46614 hom., cov: 35)
  • Exomes 𝑓: 0.75 (410618 hom.)
• Consequence: TCF19 NM_007109.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0155858E-6).
• BP6: Variant 6-31161839-A-G is Benign according to our data. Variant chr6-31161839-A-G is described in ClinVar as [Benign]. Clinvar id is 1181041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF19	NM_007109.3	c.631A>G	p.Met211Val	missense_variant	Exon 3 of 4	ENST00000376257.8	NP_009040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8	c.631A>G	p.Met211Val	missense_variant	Exon 3 of 4	1	NM_007109.3	ENSP00000365433.3

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118742 AN: 152140 Hom.: 46575 Cov.: 35

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.816

GnomAD2 exomes AF: 0.752 AC: 183042 AN: 243358 AF XY: 0.752

Gnomad AFR exome AF: 0.847

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.699

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.749 AC: 1092964 AN: 1459722 Hom.: 410618 Cov.: 83 AF XY: 0.748 AC XY: 542922 AN XY: 726124

African (AFR) AF: 0.851 AC: 28491 AN: 33462

American (AMR) AF: 0.771 AC: 34334 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 22402 AN: 26112

East Asian (EAS) AF: 0.647 AC: 25665 AN: 39648

South Asian (SAS) AF: 0.712 AC: 61405 AN: 86184

European-Finnish (FIN) AF: 0.741 AC: 38703 AN: 52222

Middle Eastern (MID) AF: 0.831 AC: 4789 AN: 5760

European-Non Finnish (NFE) AF: 0.748 AC: 831041 AN: 1111426

Other (OTH) AF: 0.764 AC: 46134 AN: 60348

GnomAD4 genome AF: 0.780 AC: 118835 AN: 152258 Hom.: 46614 Cov.: 35 AF XY: 0.779 AC XY: 58016 AN XY: 74438

African (AFR) AF: 0.847 AC: 35214 AN: 41568

American (AMR) AF: 0.805 AC: 12318 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2993 AN: 3472

East Asian (EAS) AF: 0.678 AC: 3501 AN: 5166

South Asian (SAS) AF: 0.687 AC: 3318 AN: 4828

European-Finnish (FIN) AF: 0.749 AC: 7933 AN: 10592

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50839 AN: 68004

Other (OTH) AF: 0.816 AC: 1724 AN: 2114

Alfa AF: 0.763 Hom.: 188732

Bravo AF: 0.790

TwinsUK AF: 0.737 AC: 2734

ALSPAC AF: 0.750 AC: 2891

ESP6500AA AF: 0.863 AC: 2183

ESP6500EA AF: 0.757 AC: 3834

ExAC AF: 0.751 AC: 87316

Asia WGS AF: 0.755 AC: 2626 AN: 3478

EpiCase AF: 0.768

EpiControl AF: 0.781

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29632382) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.48
DEOGEN2	Benign	0.00089	T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.11	.;T;T
MetaRNN	Benign	0.0000010	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.2	N;N;.
PhyloP100		1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.35	N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.012
MPC		0.51
ClinPred		0.0048	T
GERP RS		4.5
PromoterAI		0.059	Neutral
Varity_R		0.039
gMVP		0.093
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV105012451; COSMIC: COSV105012451;