chr2-74490025-G-A

Variant summary

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

The NM_022492.6(TTC31):​c.130G>A​(p.Asp44Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,544,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

TTC31
NM_022492.6 missense, splice_region

Scores

1
4
14
Splicing: ADA: 0.7487
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Publications

0 publications found
Variant links:
Genes affected
TTC31 (HGNC:25759): (tetratricopeptide repeat domain 31)

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=0.17888498).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTC31NM_022492.6 linkc.130G>A p.Asp44Asn missense_variant, splice_region_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
TTC31ENST00000233623.11 linkc.130G>A p.Asp44Asn missense_variant, splice_region_variant Exon 3 of 13 1 NM_022492.6 ENSP00000233623.6 Q49AM3-1

Frequencies

GnomAD3 genomes
AF:
0.0000330
AC:
5
AN:
151324
Hom.:
0
Cov.:
32
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:
0.0000738
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000627
AC:
1
AN:
159382
AF XY:
0.0000118
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000158
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000538
AC:
75
AN:
1393002
Hom.:
0
Cov.:
32
AF XY:
0.0000553
AC XY:
38
AN XY:
687626
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31640
American (AMR)
AF:
0.0000279
AC:
1
AN:
35818
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24946
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36256
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79278
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49514
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5280
European-Non Finnish (NFE)
AF:
0.0000690
AC:
74
AN:
1072614
Other (OTH)
AF:
0.00
AC:
0
AN:
57656
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.0000330
AC:
5
AN:
151324
Hom.:
0
Cov.:
32
AF XY:
0.0000271
AC XY:
2
AN XY:
73932
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41096
American (AMR)
AF:
0.00
AC:
0
AN:
15208
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3442
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4792
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10592
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000738
AC:
5
AN:
67716
Other (OTH)
AF:
0.00
AC:
0
AN:
2072
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000282
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000884
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 20, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.130G>A (p.D44N) alteration is located in exon 3 (coding exon 3) of the TTC31 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the aspartic acid (D) at amino acid position 44 to be replaced by an asparagine (N). 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
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0034
.;.;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.72
T;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.;L
PhyloP100
1.9
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.6
.;N;N
REVEL
Benign
0.070
Sift
Benign
0.16
.;T;T
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.96
.;.;D
Vest4
0.25
MutPred
0.35
Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP
0.62
MPC
0.091
ClinPred
0.45
T
GERP RS
3.5
Varity_R
0.058
gMVP
0.36
Mutation Taster
=77/23
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.75
dbscSNV1_RF
Benign
0.51
SpliceAI score (max)
0.15
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs769365787; hg19: chr2-74717152; COSMIC: COSV107234805; COSMIC: COSV107234805; API