14-90610819-C-A

Variant names:

• chr14-90610819-C-A
• NM_001010854.2:c.1889G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001010854.2(TTC7B):​c.1889G>T​(p.Ser630Ile) variant causes a missense change involving the alteration of a 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: TTC7B NM_001010854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63

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 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity TTC7B_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7B	NM_001010854.2	c.1889G>T	p.Ser630Ile	missense_variant	Exon 17 of 20	ENST00000328459.11	NP_001010854.1
TTC7B	NM_001401365.1	c.1889G>T	p.Ser630Ile	missense_variant	Exon 17 of 22		NP_001388294.1
TTC7B	NM_001320421.2	c.1583G>T	p.Ser528Ile	missense_variant	Exon 17 of 21		NP_001307350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7B	ENST00000328459.11	c.1889G>T	p.Ser630Ile	missense_variant	Exon 17 of 20	1	NM_001010854.2	ENSP00000336127.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1889G>T (p.S630I) alteration is located in exon 17 (coding exon 17) of the TTC7B gene. This alteration results from a G to T substitution at nucleotide position 1889, causing the serine (S) at amino acid position 630 to be replaced by an isoleucine (I). 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	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Uncertain	-0.070	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.76
MutPred		0.44		Gain of catalytic residue at G626 (P = 0.0021);.;.;
MVP		0.65
MPC		0.83
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.67
gMVP		0.60

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: chr14-91077163;