14-90593520-GGG-AGT

Variant names:

• chr14-90593520-GGG-AGT
• NM_001010854.2:c.2071_2073delCCCinsACT
• TTC7B p.Pro691Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001010854.2(TTC7B):​c.2071_2073delCCCinsACT​(p.Pro691Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P691S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC7B NM_001010854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.69
• Publications: 0 publications found

Genes affected

TTC7B (HGNC:19858): (tetratricopeptide repeat domain 7B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010854.2. 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
	TTC7B	NM_001010854.2	MANE Select	c.2071_2073delCCCinsACT	p.Pro691Thr	missense	N/A	NP_001010854.1	Q86TV6-1
	TTC7B	NM_001401365.1		c.2284_2286delCCCinsACT	p.Pro762Thr	missense	N/A	NP_001388294.1
	TTC7B	NM_001320421.2		c.1816_1818delCCCinsACT	p.Pro606Thr	missense	N/A	NP_001307350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7B	ENST00000328459.11	TSL:1 MANE Select	c.2071_2073delCCCinsACT	p.Pro691Thr	missense	N/A	ENSP00000336127.4	Q86TV6-1
	TTC7B	ENST00000553972.5	TSL:1	c.532_534delCCCinsACT	p.Pro178Thr	missense	N/A	ENSP00000451440.1	A0A0C4DGK5
	TTC7B	ENST00000963264.1		c.2233_2235delCCCinsACT	p.Pro745Thr	missense	N/A	ENSP00000633323.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.7

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: chr14-91059864;