14-90541454-C-A

Variant summary

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

The NM_001010854.2(TTC7B):c.2446G>T(p.Ala816Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC7B NM_001010854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88

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

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	UniProt
TTC7B	NM_001010854.2	c.2446G>T	p.Ala816Ser	missense_variant	20/20	ENST00000328459.11
TTC7B	NM_001401365.1	c.2659G>T	p.Ala887Ser	missense_variant	22/22
TTC7B	NM_001320421.2	c.2191G>T	p.Ala731Ser	missense_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC7B	ENST00000328459.11	c.2446G>T	p.Ala816Ser	missense_variant	20/20	1	NM_001010854.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.2446G>T (p.A816S) alteration is located in exon 20 (coding exon 20) of the TTC7B gene. This alteration results from a G to T substitution at nucleotide position 2446, causing the alanine (A) at amino acid position 816 to be replaced by a serine (S). 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	Benign	0.12
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
Cadd	Uncertain	24
Dann	Benign	0.97
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.39
Sift	Benign	0.059	T;T
Sift4G	Benign	0.091	T;T
Polyphen		0.63	P;.
Vest4		0.41
MutPred		0.42		Gain of catalytic residue at F821 (P = 0.0128);.;
MVP		0.40
MPC		0.60
ClinPred		0.53	D
GERP RS		5.7
Varity_R		0.39
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-91007798;