1-100102675-CAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chr1-100102675-C-CAAAA
• rs67844941
• NM_194292.3:c.1674+276_1674+279dupTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_194292.3(SASS6):​c.1674+276_1674+279dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 70,100 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 0.00037 (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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000371 (26/70100) while in subpopulation SAS AF = 0.00161 (3/1868). AF 95% confidence interval is 0.000502. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASS6	NM_194292.3	c.1674+276_1674+279dupTTTT		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+280insTTTT		intron_variant	Intron 14 of 16	1	NM_194292.3	ENSP00000287482.5
SASS6	ENST00000462159.1	n.1907+279_1907+280insTTTT		intron_variant	Intron 13 of 15	1

Frequencies

GnomAD3 genomes AF: 0.000385 AC: 27 AN: 70100 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000802

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00159

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.000212

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000371 AC: 26 AN: 70100 Hom.: 0 Cov.: 21 AF XY: 0.000434 AC XY: 14 AN XY: 32276

African (AFR) AF: 0.000801 AC: 16 AN: 19974

American (AMR) AF: 0.00 AC: 0 AN: 6600

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2974

South Asian (SAS) AF: 0.00161 AC: 3 AN: 1868

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 120

European-Non Finnish (NFE) AF: 0.000212 AC: 7 AN: 33052

Other (OTH) AF: 0.00 AC: 0 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

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;