Genetic Variant SASS6:c.1674+279delT (chr1-100102675-CA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_194292.3(SASS6):c.1674+279delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 70,096 control chromosomes in the GnomAD database, including 190 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.058 ( 190 hom., cov: 21)

Consequence

SASS6
NM_194292.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.155

Publications

0 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), Ambry Genetics, G2P
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 -10 ACMG points.

BP6

Variant 1-100102675-CA-C is Benign according to our data. Variant chr1-100102675-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1238446.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASS6	NM_194292.3 link	c.1674+279delT		intron_variant	Intron 14 of 16	ENST00000287482.6	NP_919268.1	Q6UVJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SASS6	ENST00000287482.6 link	c.1674+279delT		intron_variant	Intron 14 of 16	1	NM_194292.3	ENSP00000287482.5		Q6UVJ0
SASS6	ENST00000462159.1 link	n.1907+279delT		intron_variant	Intron 13 of 15	1

Frequencies

GnomAD3 genomes

AF:

0.0582

AC:

4082

AN:

70098

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0431

Gnomad MID

AF:

0.0154

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0582

AC:

4078

AN:

70096

Hom.:

190

Cov.:

AF XY:

0.0630

AC XY:

2032

AN XY:

32268

show subpopulations

African (AFR)

AF:

0.0119

AC:

238

AN:

19978

American (AMR)

AF:

0.179

AC:

1181

AN:

6604

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

AN:

1616

East Asian (EAS)

AF:

0.399

AC:

1188

AN:

2976

South Asian (SAS)

AF:

0.0322

AC:

AN:

1866

European-Finnish (FIN)

AF:

0.0431

AC:

110

AN:

2554

Middle Eastern (MID)

AF:

0.00833

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.0360

AC:

1189

AN:

33046

Other (OTH)

AF:

0.0706

AC:

AN:

906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

132

264

396

528

660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 20, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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1-100102675-CAAAAAAAAAA-CAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over