NM_194292.3:c.86G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_194292.3(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. 15/21 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
NM_194292.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.01

Publications

4 publications found

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]

SASS6 Gene-Disease associations (from GenCC):

microcephaly 14, primary, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SASS6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194292.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SASS6	NM_194292.3	MANE Select	c.86G>A	p.Ser29Asn	missense	Exon 2 of 17	NP_919268.1	Q6UVJ0
	SASS6	NM_001304829.2		c.-336G>A		5_prime_UTR	Exon 2 of 16	NP_001291758.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SASS6	ENST00000287482.6	TSL:1 MANE Select	c.86G>A	p.Ser29Asn	missense	Exon 2 of 17	ENSP00000287482.5	Q6UVJ0
	SASS6	ENST00000462159.1	TSL:1	n.227G>A		non_coding_transcript_exon	Exon 2 of 16

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152188

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00101

AC:

231

AN:

228388

AF XY:

0.00133

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:

0.00000933

Gnomad OTH exome

AF:

0.000555

GnomAD4 exome

AF:

0.000589

AC:

828

AN:

1405080

Hom.:

Cov.:

AF XY:

0.000857

AC XY:

601

AN XY:

701114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31232

American (AMR)

AF:

0.00

AC:

AN:

38084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25270

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38316

South Asian (SAS)

AF:

0.00971

AC:

791

AN:

81476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53182

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00000559

AC:

AN:

1073548

Other (OTH)

AF:

0.000497

AC:

AN:

58322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000427

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0130

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000517

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00128

AC:

156

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microcephaly 14, primary, autosomal recessive (1)

not provided (1)

not specified (1)

SASS6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0040

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

PhyloP100

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

0.030

REVEL

Benign

0.052

Sift

Benign

0.77

Sift4G

Benign

0.30

Polyphen

0.023

Vest4

0.17

MVP

0.27

MPC

0.19

ClinPred

0.017

GERP RS

4.1

Varity_R

0.17

gMVP

0.24

Mutation Taster

=296/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over