dbSNP rs1673642982: TTC31:p.Asp47Ala (chr2-74490035-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022492.6(TTC31):c.140A>C(p.Asp47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,239,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

TTC31
NM_022492.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0660

Publications

0 publications found

Variant links:

Genes affected

TTC31 (HGNC:25759): (tetratricopeptide repeat domain 31)

TTC31 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20647195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC31	NM_022492.6 link	c.140A>C	p.Asp47Ala	missense_variant	Exon 3 of 13	ENST00000233623.11	NP_071937.4	Q49AM3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC31	ENST00000233623.11 link	c.140A>C	p.Asp47Ala	missense_variant	Exon 3 of 13	1	NM_022492.6	ENSP00000233623.6		Q49AM3-1

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1091038

Hom.:

Cov.:

AF XY:

0.00000366

AC XY:

AN XY:

546944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24876

American (AMR)

AF:

0.00

AC:

AN:

32734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19806

East Asian (EAS)

AF:

0.00

AC:

AN:

26028

South Asian (SAS)

AF:

0.00

AC:

AN:

74710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4594

European-Non Finnish (NFE)

AF:

0.00000241

AC:

AN:

828924

Other (OTH)

AF:

0.00

AC:

AN:

43694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148834

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40790

American (AMR)

AF:

0.00

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

4860

South Asian (SAS)

AF:

0.00

AC:

AN:

4498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67080

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 03, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.140A>C (p.D47A) alteration is located in exon 3 (coding exon 3) of the TTC31 gene. This alteration results from a A to C substitution at nucleotide position 140, causing the aspartic acid (D) at amino acid position 47 to be replaced by an alanine (A). 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

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.012

.;.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L

PhyloP100

-0.066

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

.;D;N

REVEL

Benign

0.050

Sift

Uncertain

0.0090

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.61

.;.;P

Vest4

0.45

MutPred

0.41

Loss of disorder (P = 0.0815);Loss of disorder (P = 0.0815);Loss of disorder (P = 0.0815);

MVP

0.63

MPC

0.30

ClinPred

0.92

GERP RS

0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.079

gMVP

0.49

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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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rs1673642982

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over