Genetic Variant TTC7B:p.Leu742Val (chr14-90578192-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001010854.2(TTC7B):c.2224C>G(p.Leu742Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. L742I) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TTC7B
NM_001010854.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.10

Publications

0 publications found

Variant links:

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]

TTC7B links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.283235).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC7B	NM_001010854.2	MANE Select	c.2224C>G	p.Leu742Val	missense	Exon 19 of 20	NP_001010854.1	Q86TV6-1
TTC7B	NM_001401365.1		c.2437C>G	p.Leu813Val	missense	Exon 21 of 22	NP_001388294.1
TTC7B	NM_001320421.2		c.1969C>G	p.Leu657Val	missense	Exon 20 of 21	NP_001307350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC7B	ENST00000328459.11	TSL:1 MANE Select	c.2224C>G	p.Leu742Val	missense	Exon 19 of 20	ENSP00000336127.4	Q86TV6-1
TTC7B	ENST00000553972.5	TSL:1	c.685C>G	p.Leu229Val	missense	Exon 6 of 7	ENSP00000451440.1	A0A0C4DGK5
TTC7B	ENST00000963264.1		c.2386C>G	p.Leu796Val	missense	Exon 20 of 21	ENSP00000633323.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

M_CAP

Benign

0.022

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.5

PhyloP100

8.1

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.39

REVEL

Benign

0.17

Sift

Benign

0.73

Sift4G

Benign

0.49

Polyphen

1.0

Vest4

0.68

MutPred

0.44

Gain of catalytic residue at L742 (P = 0.0126)

MVP

0.17

MPC

0.86

ClinPred

0.75

GERP RS

5.3

Varity_R

0.24

gMVP

0.25

Mutation Taster

=56/44

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over