chr16-1534549-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024600.6(TMEM204):​c.274G>A​(p.Val92Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,602,892 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TMEM204
NM_024600.6 missense

Scores

6
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52
Variant links:
Genes affected
TMEM204 (HGNC:14158): (transmembrane protein 204) C16ORF30 plays a role in cell adhesion and cellular permeability at adherens junctions (Kearsey et al., 2004 [PubMed 15206924]).[supplied by OMIM, Mar 2008]
IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2770886).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM204NM_024600.6 linkc.274G>A p.Val92Ile missense_variant 1/3 ENST00000566264.2 NP_078876.2 Q9BSN7
IFT140NM_014714.4 linkc.2400-7753C>T intron_variant ENST00000426508.7 NP_055529.2 Q96RY7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM204ENST00000566264.2 linkc.274G>A p.Val92Ile missense_variant 1/31 NM_024600.6 ENSP00000454945.1 Q9BSN7
IFT140ENST00000426508.7 linkc.2400-7753C>T intron_variant 5 NM_014714.4 ENSP00000406012.2 Q96RY7-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152224
Hom.:
0
Cov.:
33
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000378
AC:
9
AN:
238072
Hom.:
0
AF XY:
0.0000230
AC XY:
3
AN XY:
130370
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000392
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000168
GnomAD4 exome
AF:
0.0000152
AC:
22
AN:
1450668
Hom.:
0
Cov.:
32
AF XY:
0.00000692
AC XY:
5
AN XY:
722180
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152224
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000413
AC:
5

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 GeneticsMay 13, 2024The c.274G>A (p.V92I) alteration is located in exon 1 (coding exon 1) of the TMEM204 gene. This alteration results from a G to A substitution at nucleotide position 274, causing the valine (V) at amino acid position 92 to be replaced by an isoleucine (I). 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
0.29
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.26
T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
.;D
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.2
M;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.99
N;N
REVEL
Uncertain
0.31
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.51
MutPred
0.26
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
0.043
MPC
0.96
ClinPred
0.51
D
GERP RS
5.2
Varity_R
0.52
gMVP
0.55

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: rs774099296; hg19: chr16-1584550; COSMIC: COSV54152563; COSMIC: COSV54152563; API