rs150589706

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000287482.6(SASS6):​c.86G>A​(p.Ser29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000573 in 1,557,386 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00059 ( 10 hom. )

Consequence

SASS6
ENST00000287482.6 missense

Scores

1
17

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.01
Variant links:
Genes affected
SASS6 (HGNC:25403): (SAS-6 centriolar assembly protein) The protein encoded by this gene is a central component of centrioles and is necessary for their duplication and function. Centrioles adopt a cartwheel-shaped structure, with the encoded protein forming the hub and spokes inside a microtubule cylinder. Defects in this gene are a cause of autosomal recessive primary microcephaly. [provided by RefSeq, Oct 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0051552355).
BP6
Variant 1-100125922-C-T is Benign according to our data. Variant chr1-100125922-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 436635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000427 (65/152306) while in subpopulation SAS AF= 0.013 (63/4828). AF 95% confidence interval is 0.0105. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SASS6NM_194292.3 linkuse as main transcriptc.86G>A p.Ser29Asn missense_variant 2/17 ENST00000287482.6 NP_919268.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SASS6ENST00000287482.6 linkuse as main transcriptc.86G>A p.Ser29Asn missense_variant 2/171 NM_194292.3 ENSP00000287482 P1
SASS6ENST00000462159.1 linkuse as main transcriptn.227G>A non_coding_transcript_exon_variant 2/161

Frequencies

GnomAD3 genomes
AF:
0.000427
AC:
65
AN:
152188
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:
0.000192
Gnomad SAS
AF:
0.0130
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00101
AC:
231
AN:
228388
Hom.:
1
AF XY:
0.00133
AC XY:
165
AN XY:
124226
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 SAS exome
AF:
0.00841
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000933
Gnomad OTH exome
AF:
0.000555
GnomAD4 exome
AF:
0.000589
AC:
828
AN:
1405080
Hom.:
10
Cov.:
24
AF XY:
0.000857
AC XY:
601
AN XY:
701114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000261
Gnomad4 SAS exome
AF:
0.00971
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000559
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
AF:
0.000427
AC:
65
AN:
152306
Hom.:
0
Cov.:
33
AF XY:
0.000577
AC XY:
43
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0130
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000831
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00128
AC:
156
Asia WGS
AF:
0.00404
AC:
14
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoApr 25, 2017- -
SASS6-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJun 06, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Microcephaly 14, primary, autosomal recessive Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
17
DANN
Benign
0.85
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.61
T
MetaRNN
Benign
0.0052
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.49
N
MutationTaster
Benign
0.76
D;D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
0.030
N
REVEL
Benign
0.052
Sift
Benign
0.77
T
Sift4G
Benign
0.30
T
Polyphen
0.023
B
Vest4
0.17
MVP
0.27
MPC
0.19
ClinPred
0.017
T
GERP RS
4.1
Varity_R
0.17
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs150589706; hg19: chr1-100591478; API