10-5727115-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001321783.2(TASOR2):ā€‹c.479T>Cā€‹(p.Leu160Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00014 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

TASOR2
NM_001321783.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
TASOR2 (HGNC:23484): (transcription activation suppressor family member 2) Located in cytosol and nucleoplasm. [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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03688091).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TASOR2NM_001321783.2 linkuse as main transcriptc.479T>C p.Leu160Pro missense_variant 11/22 ENST00000695737.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TASOR2ENST00000695737.1 linkuse as main transcriptc.479T>C p.Leu160Pro missense_variant 11/22 NM_001321783.2 Q5VWN6-1
ENST00000411512.2 linkuse as main transcriptn.222-14427A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152250
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000506
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:
0.00
GnomAD3 exomes
AF:
0.0000281
AC:
7
AN:
249324
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135270
show subpopulations
Gnomad AFR exome
AF:
0.000387
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:
0.000165
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461790
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152250
Hom.:
0
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.000506
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:
0.00
Alfa
AF:
0.0000387
Hom.:
0
Bravo
AF:
0.000117
ESP6500AA
AF:
0.000256
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000414
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 GeneticsNov 17, 2023The c.479T>C (p.L160P) alteration is located in exon 10 (coding exon 7) of the FAM208B gene. This alteration results from a T to C substitution at nucleotide position 479, causing the leucine (L) at amino acid position 160 to be replaced by a proline (P). 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
0.058
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.093
DANN
Benign
0.60
DEOGEN2
Benign
0.0015
T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.40
T;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.037
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.5
L;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.91
N;.
REVEL
Benign
0.0030
Sift
Benign
0.17
T;.
Sift4G
Benign
0.22
T;.
Polyphen
0.0010
B;.
Vest4
0.10
MVP
0.043
MPC
0.062
ClinPred
0.018
T
GERP RS
-8.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.052
gMVP
0.32

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: rs371745457; hg19: chr10-5769078; API