15-66337016-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017858.3(TIPIN):ā€‹c.848T>Cā€‹(p.Phe283Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,613,768 control chromosomes in the GnomAD database, including 2 homozygotes. 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‘“: 0.00039 ( 2 hom. )

Consequence

TIPIN
NM_017858.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.266
Variant links:
Genes affected
TIPIN (HGNC:30750): (TIMELESS interacting protein) The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA replication. It binds TIM, which is involved in circadian rhythm regulation, and aids in protecting cells against DNA damage and stress. Two pseudogenes and two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.058361977).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TIPINNM_017858.3 linkuse as main transcriptc.848T>C p.Phe283Ser missense_variant 8/8 ENST00000261881.9 NP_060328.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TIPINENST00000261881.9 linkuse as main transcriptc.848T>C p.Phe283Ser missense_variant 8/81 NM_017858.3 ENSP00000261881 P1
TIPINENST00000562124.5 linkuse as main transcriptc.848T>C p.Phe283Ser missense_variant 8/85 ENSP00000457406
TIPINENST00000566524.5 linkuse as main transcriptc.*547T>C 3_prime_UTR_variant, NMD_transcript_variant 7/72 ENSP00000455656

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000279
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000994
AC:
25
AN:
251390
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.000167
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000393
AC:
574
AN:
1461570
Hom.:
2
Cov.:
30
AF XY:
0.000377
AC XY:
274
AN XY:
727046
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000480
Gnomad4 OTH exome
AF:
0.000513
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000248
Hom.:
0
Bravo
AF:
0.000136
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.000273
EpiControl
AF:
0.000296

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 GeneticsOct 27, 2021The c.848T>C (p.F283S) alteration is located in exon 8 (coding exon 7) of the TIPIN gene. This alteration results from a T to C substitution at nucleotide position 848, causing the phenylalanine (F) at amino acid position 283 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
Benign
0.15
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
6.5
DANN
Benign
0.93
DEOGEN2
Benign
0.0039
T;.
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.095
N
LIST_S2
Benign
0.44
T;T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.058
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.3
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.70
N;N
REVEL
Benign
0.056
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.074
T;.
Polyphen
0.20
B;.
Vest4
0.26
MVP
0.25
MPC
0.17
ClinPred
0.052
T
GERP RS
1.3
Varity_R
0.093
gMVP
0.20

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: rs201129710; hg19: chr15-66629354; API