17-1707979-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164407.2(TLCD2):​c.586C>T​(p.Pro196Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000111 in 1,537,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

TLCD2
NM_001164407.2 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25
Variant links:
Genes affected
TLCD2 (HGNC:33522): (TLC domain containing 2) Involved in several processes, including membrane assembly; phospholipid homeostasis; and regulation of membrane lipid distribution. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22681132).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLCD2NM_001164407.2 linkc.586C>T p.Pro196Ser missense_variant Exon 4 of 4 ENST00000330676.8 NP_001157879.1 A6NGC4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLCD2ENST00000330676.8 linkc.586C>T p.Pro196Ser missense_variant Exon 4 of 4 2 NM_001164407.2 ENSP00000331965.6 A6NGC4

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000347
AC:
5
AN:
144090
Hom.:
0
AF XY:
0.0000390
AC XY:
3
AN XY:
76956
show subpopulations
Gnomad AFR exome
AF:
0.000658
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000505
AC:
7
AN:
1384944
Hom.:
0
Cov.:
29
AF XY:
0.00000293
AC XY:
2
AN XY:
683398
show subpopulations
Gnomad4 AFR exome
AF:
0.000222
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.000117
ExAC
AF:
0.0000400
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.586C>T (p.P196S) alteration is located in exon 4 (coding exon 4) of the TLCD2 gene. This alteration results from a C to T substitution at nucleotide position 586, causing the proline (P) at amino acid position 196 to be replaced by a serine (S). 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
0.17
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.62
D
Eigen
Benign
0.055
Eigen_PC
Benign
0.078
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.23
T
MetaSVM
Uncertain
-0.086
T
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-5.0
D
REVEL
Uncertain
0.44
Sift
Benign
0.14
T
Sift4G
Benign
0.17
T
Vest4
0.13
MutPred
0.70
Loss of loop (P = 0.0374);
MVP
0.44
ClinPred
0.19
T
GERP RS
4.8
Varity_R
0.16
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs750807867; hg19: chr17-1611273; API