Genetic Variant TTC7A:p.Val621Leu (chr2-47046373-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020458.4(TTC7A):c.1861G>T(p.Val621Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V621M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

TTC7A
NM_020458.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.71

Publications

1 publications found

Variant links:

Genes affected

TTC7A (HGNC:19750): (tetratricopeptide repeat domain 7A) This gene encodes a protein containing tetratricopeptide repeats. Mutations in this gene disrupt intestinal development and can cause early onset inflammatory bowel disease and intestinal atresia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

TTC7A links:

STPG4 (HGNC:26850): (sperm-tail PG-rich repeat containing 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in DNA demethylation of male pronucleus and positive regulation of DNA demethylation. Predicted to act upstream of or within C-5 methylation of cytosine. Predicted to be located in cytoplasm and nucleus. Predicted to be active in female pronucleus; germinal vesicle; and male pronucleus. [provided by Alliance of Genome Resources, Apr 2022]

STPG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14049804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC7A	NM_020458.4	MANE Select	c.1861G>T	p.Val621Leu	missense	Exon 16 of 20	NP_065191.2	Q9ULT0-1
TTC7A	NM_001288951.2		c.1861G>T	p.Val621Leu	missense	Exon 16 of 21	NP_001275880.1	Q9ULT0-4
TTC7A	NM_001288953.2		c.1759G>T	p.Val587Leu	missense	Exon 17 of 21	NP_001275882.1	G5E9G4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.1861G>T	p.Val621Leu	missense	Exon 16 of 20	ENSP00000316699.5	Q9ULT0-1
TTC7A	ENST00000394850.6	TSL:1	c.1861G>T	p.Val621Leu	missense	Exon 16 of 21	ENSP00000378320.2	Q9ULT0-4
TTC7A	ENST00000409825.5	TSL:1	n.*1610G>T		non_coding_transcript_exon	Exon 17 of 21	ENSP00000386521.1	H0Y3V7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

M_CAP

Benign

0.0069

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.68

PhyloP100

3.7

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.91

REVEL

Benign

0.086

Sift

Benign

0.84

Sift4G

Benign

1.0

Polyphen

0.31

Vest4

0.19

MutPred

0.33

Loss of MoRF binding (P = 0.1204)

MVP

0.42

MPC

0.064

ClinPred

0.94

GERP RS

5.5

Varity_R

0.13

gMVP

0.15

Mutation Taster

=82/18

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over