rs773717301

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032740.4(SFT2D3):​c.179C>A​(p.Ser60*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000603 in 1,327,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SFT2D3
NM_032740.4 stop_gained

Scores

2
5

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SFT2D3NM_032740.4 linkc.179C>A p.Ser60* stop_gained Exon 1 of 1 ENST00000310981.6 NP_116129.3 Q587I9
WDR33NM_018383.5 linkc.*4616G>T 3_prime_UTR_variant Exon 22 of 22 ENST00000322313.9 NP_060853.3 Q9C0J8-1
WDR33XM_011511436.2 linkc.*4616G>T 3_prime_UTR_variant Exon 22 of 22 XP_011509738.1 Q9C0J8-1
WDR33XM_005263697.4 linkc.*4786G>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
SFT2D3ENST00000310981.6 linkc.179C>A p.Ser60* stop_gained Exon 1 of 1 6 NM_032740.4 ENSP00000310803.3 Q587I9
WDR33ENST00000322313.9 linkc.*4616G>T 3_prime_UTR_variant Exon 22 of 22 1 NM_018383.5 ENSP00000325377.3 Q9C0J8-1
ENSG00000293688ENST00000718293.1 linkn.-247G>T upstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000726
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
13670
AF XY:
0.00
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:
0.00000425
AC:
5
AN:
1175862
Hom.:
0
Cov.:
31
AF XY:
0.00000349
AC XY:
2
AN XY:
573148
show subpopulations
African (AFR)
AF:
0.000171
AC:
4
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:
0.0000213
AC:
1
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:
0.00
AC:
0
AN:
975850
Other (OTH)
AF:
0.00
AC:
0
AN:
47146
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.445
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

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:
0.0000198
AC:
3
AN:
151272
Hom.:
0
Cov.:
33
AF XY:
0.0000271
AC XY:
2
AN XY:
73926
show subpopulations
African (AFR)
AF:
0.0000724
AC:
3
AN:
41420
American (AMR)
AF:
0.00
AC:
0
AN:
15184
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5156
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10220
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67708
Other (OTH)
AF:
0.00
AC:
0
AN:
2098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.608
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
36
DANN
Benign
0.96
Eigen
Benign
0.0068
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.57
D
PhyloP100
4.3
Vest4
0.0070
GERP RS
1.3
PromoterAI
0.021
Neutral
Mutation Taster
=46/154
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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