1-100102675-CAAAAAAAAAA-CAAAAAAAAAAAA

Variant names:

• chr1-100102675-C-CAA
• rs67844941
• NM_194292.3:c.1674+278_1674+279dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_194292.3(SASS6):​c.1674+278_1674+279dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 69,960 control chromosomes in the GnomAD database, including 151 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (151 hom., cov: 21)
• Consequence: SASS6 NM_194292.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.155
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-100102675-C-CAA is Benign according to our data. Variant chr1-100102675-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1271920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASS6	NM_194292.3	c.1674+278_1674+279dupTT		intron_variant	Intron 14 of 16	ENST00000287482.6	NP_919268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SASS6	ENST00000287482.6	c.1674+279_1674+280insTT		intron_variant	Intron 14 of 16	1	NM_194292.3	ENSP00000287482.5
SASS6	ENST00000462159.1	n.1907+279_1907+280insTT		intron_variant	Intron 13 of 15	1

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 4300 AN: 69960 Hom.: 151 Cov.: 21

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.00838

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0610

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

GnomAD4 genome AF: 0.0615 AC: 4303 AN: 69960 Hom.: 151 Cov.: 21 AF XY: 0.0600 AC XY: 1932 AN XY: 32198

African (AFR) AF: 0.0683 AC: 1361 AN: 19916

American (AMR) AF: 0.0498 AC: 328 AN: 6580

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 113 AN: 1612

East Asian (EAS) AF: 0.00841 AC: 25 AN: 2974

South Asian (SAS) AF: 0.0391 AC: 73 AN: 1866

European-Finnish (FIN) AF: 0.0208 AC: 53 AN: 2554

Middle Eastern (MID) AF: 0.0500 AC: 6 AN: 120

European-Non Finnish (NFE) AF: 0.0670 AC: 2211 AN: 33002

Other (OTH) AF: 0.0607 AC: 55 AN: 906

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs67844941; hg19: chr1-100568231;