rs1256915313
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_032740.4(SFT2D3):c.410G>A(p.Arg137His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,271,732 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: not found (cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
SFT2D3
NM_032740.4 missense
NM_032740.4 missense
Scores
2
1
16
Clinical Significance
Conservation
PhyloP100: 2.03
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37156335).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SFT2D3 | NM_032740.4 | c.410G>A | p.Arg137His | missense_variant | Exon 1 of 1 | ENST00000310981.6 | NP_116129.3 | |
| WDR33 | NM_018383.5 | c.*4385C>T | 3_prime_UTR_variant | Exon 22 of 22 | ENST00000322313.9 | NP_060853.3 | ||
| WDR33 | XM_011511436.2 | c.*4385C>T | 3_prime_UTR_variant | Exon 22 of 22 | XP_011509738.1 | |||
| WDR33 | XM_005263697.4 | c.*4555C>T | 3_prime_UTR_variant | Exon 21 of 21 | XP_005263754.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SFT2D3 | ENST00000310981.6 | c.410G>A | p.Arg137His | missense_variant | Exon 1 of 1 | 6 | NM_032740.4 | ENSP00000310803.3 | ||
| WDR33 | ENST00000322313.9 | c.*4385C>T | 3_prime_UTR_variant | Exon 22 of 22 | 1 | NM_018383.5 | ENSP00000325377.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000426 AC: 2AN: 46988 AF XY: 0.0000356 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
46988
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000173 AC: 22AN: 1271732Hom.: 0 Cov.: 31 AF XY: 0.0000208 AC XY: 13AN XY: 626342 show subpopulations
GnomAD4 exome
AF:
AC:
22
AN:
1271732
Hom.:
Cov.:
31
AF XY:
AC XY:
13
AN XY:
626342
show subpopulations
African (AFR)
AF:
AC:
0
AN:
24888
American (AMR)
AF:
AC:
0
AN:
18140
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
20300
East Asian (EAS)
AF:
AC:
0
AN:
26620
South Asian (SAS)
AF:
AC:
2
AN:
66574
European-Finnish (FIN)
AF:
AC:
0
AN:
31780
Middle Eastern (MID)
AF:
AC:
0
AN:
3692
European-Non Finnish (NFE)
AF:
AC:
20
AN:
1027638
Other (OTH)
AF:
AC:
0
AN:
52100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.516
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.410G>A (p.R137H) alteration is located in exon 1 (coding exon 1) of the SFT2D3 gene. This alteration results from a G to A substitution at nucleotide position 410, causing the arginine (R) at amino acid position 137 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of methylation at R137 (P = 0.0248);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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