TTC7A p.Val290Val

Variant names:

• chr2-46994380-G-G
• NM_020458.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-46994381--
• chr2-46994383-C-T
• chr2-46994383-C-A
• chr2-46994383-C-G

Variant summary

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

The NM_020458.4(TTC7A):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC7A NM_020458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• gastrointestinal defects and immunodeficiency syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• multiple intestinal atresia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen

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_020458.4. 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
	TTC7A	NM_020458.4	MANE Select	c.		intron	N/A	NP_065191.2	Q9ULT0-1
	TTC7A	NM_001288951.2		c.		intron	N/A	NP_001275880.1	Q9ULT0-4
	TTC7A	NM_001288953.2		c.		intron	N/A	NP_001275882.1	G5E9G4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.		intron	N/A	ENSP00000316699.5	Q9ULT0-1
	TTC7A	ENST00000394850.6	TSL:1	c.		intron	N/A	ENSP00000378320.2	Q9ULT0-4
	TTC7A	ENST00000484061.5	TSL:1	n.		exon_region	Exon 1 of 12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-47221519;