chr14-67472766-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001348543.2(TMEM229B):​c.*654A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,734 control chromosomes in the GnomAD database, including 1,016 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1007 hom., cov: 32)
Exomes 𝑓: 0.12 ( 9 hom. )

Consequence

TMEM229B
NM_001348543.2 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11

Publications

15 publications found
Variant links:
Genes affected
TMEM229B (HGNC:20130): (transmembrane protein 229B) Predicted to act upstream of or within response to bacterium. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]
GPHN Gene-Disease associations (from GenCC):
  • sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
    Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
  • hereditary hyperekplexia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM229BNM_001348543.2 linkc.*654A>G 3_prime_UTR_variant Exon 3 of 3 ENST00000554480.6 NP_001335472.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM229BENST00000554480.6 linkc.*654A>G 3_prime_UTR_variant Exon 3 of 3 2 NM_001348543.2 ENSP00000450859.2 Q8NBD8G3V2T8

Frequencies

GnomAD3 genomes
AF:
0.113
AC:
17078
AN:
151440
Hom.:
1005
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0899
Gnomad AMI
AF:
0.212
Gnomad AMR
AF:
0.0885
Gnomad ASJ
AF:
0.138
Gnomad EAS
AF:
0.133
Gnomad SAS
AF:
0.105
Gnomad FIN
AF:
0.114
Gnomad MID
AF:
0.130
Gnomad NFE
AF:
0.128
Gnomad OTH
AF:
0.123
GnomAD4 exome
AF:
0.116
AC:
136
AN:
1174
Hom.:
9
Cov.:
0
AF XY:
0.129
AC XY:
87
AN XY:
676
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
4
American (AMR)
AF:
0.0682
AC:
3
AN:
44
Ashkenazi Jewish (ASJ)
AF:
0.167
AC:
1
AN:
6
East Asian (EAS)
AF:
0.167
AC:
1
AN:
6
South Asian (SAS)
AF:
0.0833
AC:
1
AN:
12
European-Finnish (FIN)
AF:
0.102
AC:
50
AN:
490
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.130
AC:
73
AN:
560
Other (OTH)
AF:
0.135
AC:
7
AN:
52
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
6
12
17
23
29
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
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
GnomAD4 genome
AF:
0.113
AC:
17088
AN:
151560
Hom.:
1007
Cov.:
32
AF XY:
0.114
AC XY:
8429
AN XY:
74086
show subpopulations
African (AFR)
AF:
0.0899
AC:
3696
AN:
41104
American (AMR)
AF:
0.0883
AC:
1346
AN:
15242
Ashkenazi Jewish (ASJ)
AF:
0.138
AC:
471
AN:
3422
East Asian (EAS)
AF:
0.133
AC:
686
AN:
5158
South Asian (SAS)
AF:
0.105
AC:
507
AN:
4806
European-Finnish (FIN)
AF:
0.114
AC:
1209
AN:
10602
Middle Eastern (MID)
AF:
0.143
AC:
42
AN:
294
European-Non Finnish (NFE)
AF:
0.128
AC:
8680
AN:
67926
Other (OTH)
AF:
0.123
AC:
258
AN:
2096
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
793
1587
2380
3174
3967
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
202
404
606
808
1010
<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:
0.120
Hom.:
3466
Bravo
AF:
0.110
Asia WGS
AF:
0.100
AC:
349
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
CADD
Benign
14
DANN
Benign
0.83
PhyloP100
2.1
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs17104363; hg19: chr14-67939483; API