Genetic Variant TTC7B:p.Leu576Val (chr14-90644073-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001010854.2(TTC7B):c.1726C>G(p.Leu576Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000812 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

TTC7B
NM_001010854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

Publications

1 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:

TTC7B-AS1 (HGNC:56196): (TTC7B antisense RNA 1)

TTC7B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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_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.1726C>G	p.Leu576Val	missense	Exon 15 of 20	NP_001010854.1	Q86TV6-1
TTC7B	NM_001401365.1		c.1726C>G	p.Leu576Val	missense	Exon 15 of 22	NP_001388294.1
TTC7B	NM_001320421.2		c.1420C>G	p.Leu474Val	missense	Exon 15 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.1726C>G	p.Leu576Val	missense	Exon 15 of 20	ENSP00000336127.4	Q86TV6-1
TTC7B	ENST00000553972.5	TSL:1	c.136C>G	p.Leu46Val	missense	Exon 1 of 7	ENSP00000451440.1	A0A0C4DGK5
TTC7B-AS1	ENST00000557007.1	TSL:1	n.92-671G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000135

AC:

AN:

251414

AF XY:

0.000132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000855

AC:

125

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00325

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1112002

Other (OTH)

AF:

0.000315

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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

AF:

0.0000395

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.086

MetaSVM

Uncertain

0.075

MutationAssessor

Benign

1.7

PhyloP100

5.2

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.46

Sift

Benign

0.17

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.89

MVP

0.64

MPC

0.84

ClinPred

0.22

GERP RS

4.0

PromoterAI

0.050

Neutral

(source)

Varity_R

0.28

gMVP

0.56

Mutation Taster

=25/75

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.31

Position offset: 1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over