Variant 22-26494939-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012143.4(TFIP11):c.1850G>A(p.Gly617Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TFIP11
NM_012143.4 missense, splice_region

Scores

Splicing: ADA: 0.6773

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

TFIP11 (HGNC:17165): (tuftelin interacting protein 11) This gene encodes a protein component of the spliceosome that promotes the release of the lariat-intron during late-stage splicing through the recruitment of a pre-mRNA splicing factor called DEAH-box helicase 15. The encoded protein contains a G-patch domain, a hallmark of RNA-processing proteins, that binds DEAH-box helicase 15. This protein contains an atypical nuclear localization sequence as well as a nuclear speckle-targeting sequence, enabling it to localize to distinct speckled regions within the cell nucleus. Polymorphisms in this gene are associated with dental caries suggesting a role in amelogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

TFIP11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFIP11	NM_012143.4 linkuse as main transcript	c.1850G>A	p.Gly617Glu	missense_variant, splice_region_variant	13/15	ENST00000407690.6	NP_036275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFIP11	ENST00000407690.6 linkuse as main transcript	c.1850G>A	p.Gly617Glu	missense_variant, splice_region_variant	13/15	1	NM_012143.4	ENSP00000384421	P1	Q9UBB9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.1850G>A (p.G617E) alteration is located in exon 14 (coding exon 10) of the TFIP11 gene. This alteration results from a G to A substitution at nucleotide position 1850, causing the glycine (G) at amino acid position 617 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.89

DEOGEN2

Benign

0.036

T;T;T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.072

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

T;.;.;.;.

M_CAP

Benign

0.0038

MetaRNN

Uncertain

0.69

D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

1.7

.;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.66

.;T;T;T;T

Sift4G

Benign

0.89

T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B

Vest4

0.70

MutPred

0.73

Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.58

MPC

0.50

ClinPred

0.76

GERP RS

5.3

Varity_R

0.16

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.68

dbscSNV1_RF

Benign

0.58

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over