chr1-100102675-C-CA

Variant names:

• chr1-100102675-C-CA
• rs67844941
• NM_194292.3:c.1674+279dupT

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+279dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 69,726 control chromosomes in the GnomAD database, including 1,036 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1036 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-CA is Benign according to our data. Variant chr1-100102675-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1271552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.161 AC: 11206 AN: 69726 Hom.: 1038 Cov.: 21

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0628

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0769

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.161 AC: 11199 AN: 69726 Hom.: 1036 Cov.: 21 AF XY: 0.160 AC XY: 5127 AN XY: 32112

African (AFR) AF: 0.304 AC: 6045 AN: 19896

American (AMR) AF: 0.0802 AC: 528 AN: 6580

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 189 AN: 1606

East Asian (EAS) AF: 0.0502 AC: 149 AN: 2968

South Asian (SAS) AF: 0.0641 AC: 119 AN: 1856

European-Finnish (FIN) AF: 0.103 AC: 264 AN: 2554

Middle Eastern (MID) AF: 0.0583 AC: 7 AN: 120

European-Non Finnish (NFE) AF: 0.114 AC: 3743 AN: 32810

Other (OTH) AF: 0.141 AC: 128 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 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs67844941; hg19: chr1-100568231;