2-127701586-C-T

Variant summary

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

The NM_032740.4(SFT2D3):​c.58C>T​(p.Pro20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,359,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SFT2D3
NM_032740.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.281
Variant links:
Genes affected
SFT2D3 (HGNC:28767): (SFT2 domain containing 3) Predicted to be involved in protein transport and vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
WDR33 (HGNC:25651): (WD repeat domain 33) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is highly expressed in testis and the protein is localized to the nucleus. This gene may play important roles in the mechanisms of cytodifferentiation and/or DNA recombination. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.011706561).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SFT2D3NM_032740.4 linkuse as main transcriptc.58C>T p.Pro20Ser missense_variant 1/1 ENST00000310981.6 NP_116129.3 Q587I9
WDR33NM_018383.5 linkuse as main transcriptc.*4737G>A 3_prime_UTR_variant 22/22 ENST00000322313.9 NP_060853.3 Q9C0J8-1
WDR33XM_011511436.2 linkuse as main transcriptc.*4737G>A 3_prime_UTR_variant 22/22 XP_011509738.1 Q9C0J8-1
WDR33XM_005263697.4 linkuse as main transcriptc.*4907G>A 3_prime_UTR_variant 21/21 XP_005263754.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SFT2D3ENST00000310981.6 linkuse as main transcriptc.58C>T p.Pro20Ser missense_variant 1/16 NM_032740.4 ENSP00000310803.3 Q587I9
WDR33ENST00000322313 linkuse as main transcriptc.*4737G>A 3_prime_UTR_variant 22/221 NM_018383.5 ENSP00000325377.3 Q9C0J8-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000108
AC:
13
AN:
1207224
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
8
AN XY:
590856
show subpopulations
Gnomad4 AFR exome
AF:
0.0000413
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000360
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000111
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000108
AC:
1
Asia WGS
AF:
0.00202
AC:
7
AN:
3476

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 GeneticsJun 10, 2022The c.58C>T (p.P20S) alteration is located in exon 1 (coding exon 1) of the SFT2D3 gene. This alteration results from a C to T substitution at nucleotide position 58, causing the proline (P) at amino acid position 20 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
0.073
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
0.18
DANN
Benign
0.84
DEOGEN2
Benign
0.00087
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.32
T
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.012
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
0.91
D;N
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.011
Sift
Benign
0.38
T
Sift4G
Benign
0.78
T
Polyphen
0.0020
B
Vest4
0.039
MutPred
0.21
Gain of phosphorylation at P20 (P = 0.0222);
MVP
0.27
ClinPred
0.021
T
GERP RS
0.24
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.022
gMVP
0.26

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: rs764569227; hg19: chr2-128459160; API