chr1-32075014-C-T

Variant summary

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

The NM_001319677.2(TMEM39B):​c.-314C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000296 in 1,551,444 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TMEM39B
NM_001319677.2 5_prime_UTR_premature_start_codon_gain

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50
Variant links:
Genes affected
TMEM39B (HGNC:25510): (transmembrane protein 39B) Predicted to be integral component of membrane. Predicted to be active in 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=0.100289315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM39BNM_018056.4 linkc.68C>T p.Ser23Leu missense_variant Exon 2 of 9 ENST00000336294.10 NP_060526.2 Q9GZU3-1Q9BT39

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM39BENST00000336294.10 linkc.68C>T p.Ser23Leu missense_variant Exon 2 of 9 1 NM_018056.4 ENSP00000338165.5 Q9GZU3-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000640
AC:
10
AN:
156206
Hom.:
0
AF XY:
0.0000604
AC XY:
5
AN XY:
82786
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000459
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000828
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000286
AC:
40
AN:
1399284
Hom.:
0
Cov.:
30
AF XY:
0.0000275
AC XY:
19
AN XY:
690158
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000112
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000580
Hom.:
0
Bravo
AF:
0.0000340

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.68C>T (p.S23L) alteration is located in exon 2 (coding exon 2) of the TMEM39B gene. This alteration results from a C to T substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a leucine (L). 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
0.088
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
T;T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.056
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.84
T;D
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.46
N;N
REVEL
Benign
0.22
Sift
Benign
0.33
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.047
B;.
Vest4
0.18
MVP
0.23
MPC
0.43
ClinPred
0.070
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.14

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: rs1468009880; hg19: chr1-32540615; API