chr11-120330187-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001198671.2(TLCD5):ā€‹c.410A>Gā€‹(p.Asn137Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,578,496 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00018 ( 1 hom., cov: 32)
Exomes š‘“: 0.00023 ( 5 hom. )

Consequence

TLCD5
NM_001198671.2 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21
Variant links:
Genes affected
TLCD5 (HGNC:28280): (TLC domain containing 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.072579324).
BS2
High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TLCD5NM_001198671.2 linkuse as main transcriptc.410A>G p.Asn137Ser missense_variant 3/3 ENST00000375095.3 NP_001185600.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TLCD5ENST00000375095.3 linkuse as main transcriptc.410A>G p.Asn137Ser missense_variant 3/32 NM_001198671.2 ENSP00000364236 P1Q6ZRR5-1
TLCD5ENST00000529187.1 linkuse as main transcriptc.338+138A>G intron_variant 1 ENSP00000434862 Q6ZRR5-4
TLCD5ENST00000314475.6 linkuse as main transcriptc.476A>G p.Asn159Ser missense_variant 3/32 ENSP00000312672 Q6ZRR5-3
TLCD5ENST00000531346.1 linkuse as main transcriptn.284A>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.000178
AC:
27
AN:
152052
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00230
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00291
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.000419
AC:
81
AN:
193328
Hom.:
1
AF XY:
0.000514
AC XY:
53
AN XY:
103024
show subpopulations
Gnomad AFR exome
AF:
0.0000832
Gnomad AMR exome
AF:
0.0000369
Gnomad ASJ exome
AF:
0.00154
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00218
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.000579
GnomAD4 exome
AF:
0.000234
AC:
334
AN:
1426326
Hom.:
5
Cov.:
31
AF XY:
0.000293
AC XY:
207
AN XY:
706228
show subpopulations
Gnomad4 AFR exome
AF:
0.0000304
Gnomad4 AMR exome
AF:
0.0000782
Gnomad4 ASJ exome
AF:
0.00180
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00254
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000476
Gnomad4 OTH exome
AF:
0.000236
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152170
Hom.:
1
Cov.:
32
AF XY:
0.000255
AC XY:
19
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00230
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00291
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.000470
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.000338
AC:
40
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 09, 2023The c.476A>G (p.N159S) alteration is located in exon 3 (coding exon 2) of the TMEM136 gene. This alteration results from a A to G substitution at nucleotide position 476, causing the asparagine (N) at amino acid position 159 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
Uncertain
0.50
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
D;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.073
T;T
MetaSVM
Uncertain
0.0014
D
MutationAssessor
Benign
1.9
L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Uncertain
0.60
Sift
Benign
0.095
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.74
MVP
0.70
MPC
0.41
ClinPred
0.076
T
GERP RS
4.9
Varity_R
0.17
gMVP
0.81

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

LitVar

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

Other links and lift over

dbSNP: rs527644222; hg19: chr11-120200896; API