1-100102675-CAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

• chr1-100102675-C-CAAAAAAA
• rs67844941
• NM_194292.3:c.1674+273_1674+279dupTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_194292.3(SASS6):​c.1674+273_1674+279dupTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 70,116 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000014 (0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASS6	NM_194292.3	c.1674+273_1674+279dupTTTTTTT		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+280insTTTTTTT		intron_variant	Intron 14 of 16	1	NM_194292.3	ENSP00000287482.5
SASS6	ENST00000462159.1	n.1907+279_1907+280insTTTTTTT		intron_variant	Intron 13 of 15	1

Frequencies

GnomAD3 genomes AF: 0.0000143 AC: 1 AN: 70116 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000302

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000143 AC: 1 AN: 70116 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 32260

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19952

American (AMR) AF: 0.00 AC: 0 AN: 6590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1616

East Asian (EAS) AF: 0.00 AC: 0 AN: 2984

South Asian (SAS) AF: 0.00 AC: 0 AN: 1884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 130

European-Non Finnish (NFE) AF: 0.0000302 AC: 1 AN: 33068

Other (OTH) AF: 0.00 AC: 0 AN: 904

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15

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;