1-100102675-CAAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr1-100102675-C-CAAA
• rs67844941
• NM_194292.3:c.1674+277_1674+279dupTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_194292.3(SASS6):​c.1674+277_1674+279dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 69,960 control chromosomes in the GnomAD database, including 156 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.065 (156 hom., cov: 21)
• Consequence: SASS6 NM_194292.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASS6	NM_194292.3	c.1674+277_1674+279dupTTT		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+280insTTT		intron_variant	Intron 14 of 16	1	NM_194292.3	ENSP00000287482.5
SASS6	ENST00000462159.1	n.1907+279_1907+280insTTT		intron_variant	Intron 13 of 15	1

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 4564 AN: 69960 Hom.: 155 Cov.: 21

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.0884

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0223

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0231

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.0597

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

GnomAD4 genome AF: 0.0654 AC: 4572 AN: 69960 Hom.: 156 Cov.: 21 AF XY: 0.0643 AC XY: 2072 AN XY: 32212

African (AFR) AF: 0.0777 AC: 1548 AN: 19920

American (AMR) AF: 0.0394 AC: 259 AN: 6580

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 36 AN: 1614

East Asian (EAS) AF: 0.0138 AC: 41 AN: 2974

South Asian (SAS) AF: 0.0687 AC: 128 AN: 1864

European-Finnish (FIN) AF: 0.0333 AC: 85 AN: 2552

Middle Eastern (MID) AF: 0.0250 AC: 3 AN: 120

European-Non Finnish (NFE) AF: 0.0721 AC: 2380 AN: 32998

Other (OTH) AF: 0.0595 AC: 54 AN: 908

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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;