chr22-26503508-T-C

Variant names:

• chr22-26503508-T-C
• rs134136
• NM_012143.4:c.648+158A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012143.4(TFIP11):​c.648+158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,016 control chromosomes in the GnomAD database, including 33,615 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33615 hom., cov: 32)
• Consequence: TFIP11 NM_012143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFIP11	NM_012143.4	c.648+158A>G		intron_variant	Intron 7 of 14	ENST00000407690.6	NP_036275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFIP11	ENST00000407690.6	c.648+158A>G		intron_variant	Intron 7 of 14	1	NM_012143.4	ENSP00000384421.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100520 AN: 151898 Hom.: 33593 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.668

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100578 AN: 152016 Hom.: 33615 Cov.: 32 AF XY: 0.660 AC XY: 49056 AN XY: 74286

African (AFR) AF: 0.743 AC: 30801 AN: 41454

American (AMR) AF: 0.627 AC: 9577 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2510 AN: 3468

East Asian (EAS) AF: 0.669 AC: 3457 AN: 5164

South Asian (SAS) AF: 0.530 AC: 2554 AN: 4822

European-Finnish (FIN) AF: 0.682 AC: 7194 AN: 10552

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42299 AN: 67968

Other (OTH) AF: 0.665 AC: 1405 AN: 2114

Alfa AF: 0.644 Hom.: 6982

Bravo AF: 0.662

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.42
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs134136; hg19: chr22-26899474;