1-100109436-C-T

Variant names:

• chr1-100109436-C-T
• rs640030
• NM_194292.3:c.861+856G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194292.3(SASS6):​c.861+856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,784 control chromosomes in the GnomAD database, including 47,713 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (47713 hom., cov: 30)
• Consequence: SASS6 NM_194292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 5 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), PanelApp Australia, G2P, Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194292.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SASS6	NM_194292.3	MANE Select	c.861+856G>A		intron	N/A	NP_919268.1	Q6UVJ0
	SASS6	NM_001304829.2		c.360+856G>A		intron	N/A	NP_001291758.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SASS6	ENST00000287482.6	TSL:1 MANE Select	c.861+856G>A		intron	N/A	ENSP00000287482.5	Q6UVJ0
	SASS6	ENST00000462159.1	TSL:1	n.1002+856G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118440 AN: 151666 Hom.: 47699 Cov.: 30

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.781 AC: 118496 AN: 151784 Hom.: 47713 Cov.: 30 AF XY: 0.786 AC XY: 58349 AN XY: 74220

African (AFR) AF: 0.561 AC: 23225 AN: 41370

American (AMR) AF: 0.862 AC: 13146 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3085 AN: 3462

East Asian (EAS) AF: 0.943 AC: 4883 AN: 5176

South Asian (SAS) AF: 0.897 AC: 4323 AN: 4818

European-Finnish (FIN) AF: 0.887 AC: 9392 AN: 10588

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57751 AN: 67810

Other (OTH) AF: 0.810 AC: 1702 AN: 2102

Alfa AF: 0.833 Hom.: 27220

Bravo AF: 0.770

Asia WGS AF: 0.876 AC: 3047 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.31
PhyloP100		-0.11
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: rs640030; hg19: chr1-100574992;