19-3543317-C-T

Variant summary

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

The NM_001135580.2(TEKTIP1):​c.166C>T​(p.Arg56Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000671 in 1,549,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

TEKTIP1
NM_001135580.2 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0190
Variant links:
Genes affected
TEKTIP1 (HGNC:34496): (tektin bundle interacting protein 1)
MFSD12 (HGNC:28299): (major facilitator superfamily domain containing 12) Enables cysteine transmembrane transporter activity. Involved in cysteine transmembrane transport; pigment metabolic process involved in pigmentation; and regulation of melanin biosynthetic process. Located in lysosome and melanosome. Part of late endosome. [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=0.06261644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TEKTIP1NM_001135580.2 linkc.166C>T p.Arg56Trp missense_variant Exon 2 of 4 ENST00000329493.6 NP_001129052.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TEKTIP1ENST00000329493.6 linkc.166C>T p.Arg56Trp missense_variant Exon 2 of 4 2 NM_001135580.2 ENSP00000327950.4 A6NCJ1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000165
AC:
25
AN:
151914
Hom.:
0
AF XY:
0.000111
AC XY:
9
AN XY:
81068
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000731
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000132
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000512
Gnomad OTH exome
AF:
0.000233
GnomAD4 exome
AF:
0.0000651
AC:
91
AN:
1397036
Hom.:
0
Cov.:
31
AF XY:
0.0000551
AC XY:
38
AN XY:
689090
show subpopulations
Gnomad4 AFR exome
AF:
0.000158
Gnomad4 AMR exome
AF:
0.000504
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.000101
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000528
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000830
Hom.:
0
Bravo
AF:
0.000102
ExAC
AF:
0.0000368
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.166C>T (p.R56W) alteration is located in exon 2 (coding exon 2) of the C19orf71 gene. This alteration results from a C to T substitution at nucleotide position 166, causing the arginine (R) at amino acid position 56 to be replaced by a tryptophan (W). 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
0.12
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.016
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.9
L
PROVEAN
Pathogenic
-5.1
D
REVEL
Benign
0.064
Sift
Benign
0.060
T
Sift4G
Uncertain
0.0020
D
Polyphen
0.0060
B
Vest4
0.21
MVP
0.22
ClinPred
0.060
T
GERP RS
-1.4
Varity_R
0.10
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs780611465; hg19: chr19-3543315; COSMIC: COSV61536561; COSMIC: COSV61536561; API