NM_032740.4:c.179C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032740.4(SFT2D3):​c.179C>T​(p.Ser60Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000407 in 1,327,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

SFT2D3
NM_032740.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Publications

1 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.025118023).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SFT2D3NM_032740.4 linkc.179C>T p.Ser60Leu missense_variant Exon 1 of 1 ENST00000310981.6 NP_116129.3 Q587I9
WDR33NM_018383.5 linkc.*4616G>A 3_prime_UTR_variant Exon 22 of 22 ENST00000322313.9 NP_060853.3 Q9C0J8-1
WDR33XM_011511436.2 linkc.*4616G>A 3_prime_UTR_variant Exon 22 of 22 XP_011509738.1 Q9C0J8-1
WDR33XM_005263697.4 linkc.*4786G>A 3_prime_UTR_variant Exon 21 of 21 XP_005263754.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SFT2D3ENST00000310981.6 linkc.179C>T p.Ser60Leu missense_variant Exon 1 of 1 6 NM_032740.4 ENSP00000310803.3 Q587I9
WDR33ENST00000322313.9 linkc.*4616G>A 3_prime_UTR_variant Exon 22 of 22 1 NM_018383.5 ENSP00000325377.3 Q9C0J8-1
ENSG00000293688ENST00000718293.1 linkn.-247G>A upstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.0000397
AC:
6
AN:
151164
Hom.:
0
Cov.:
33
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000738
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000732
AC:
1
AN:
13670
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000408
AC:
48
AN:
1175862
Hom.:
0
Cov.:
31
AF XY:
0.0000489
AC XY:
28
AN XY:
573148
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
23430
American (AMR)
AF:
0.00
AC:
0
AN:
10366
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15822
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25826
South Asian (SAS)
AF:
0.0000852
AC:
4
AN:
46936
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
27288
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3198
European-Non Finnish (NFE)
AF:
0.0000441
AC:
43
AN:
975850
Other (OTH)
AF:
0.0000212
AC:
1
AN:
47146
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000397
AC:
6
AN:
151164
Hom.:
0
Cov.:
33
AF XY:
0.0000271
AC XY:
2
AN XY:
73808
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41302
American (AMR)
AF:
0.00
AC:
0
AN:
15164
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10220
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000738
AC:
5
AN:
67718
Other (OTH)
AF:
0.00
AC:
0
AN:
2076
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000775
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 10, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.179C>T (p.S60L) 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 179, causing the serine (S) at amino acid position 60 to be replaced by a leucine (L). 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
0.11
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
19
DANN
Benign
0.90
DEOGEN2
Benign
0.012
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.51
T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.025
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
PhyloP100
4.3
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.083
Sift
Benign
0.32
T
Sift4G
Benign
0.24
T
Polyphen
0.0070
B
Vest4
0.12
MutPred
0.25
Loss of glycosylation at S60 (P = 0.0248);
MVP
0.28
ClinPred
0.15
T
GERP RS
1.3
PromoterAI
-0.042
Neutral
Varity_R
0.041
gMVP
0.47
Mutation Taster
=70/30
polymorphism

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

Other links and lift over

dbSNP: rs773717301; hg19: chr2-128459281; API