15-75372009-GACACGAT-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_001145358.2(SIN3A):c.3785_3791del(p.Tyr1262SerfsTer70) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIN3A NM_001145358.2 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.27

Genes affected

SIN3A (HGNC:19353): (SIN3 transcription regulator family member A) The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which are important for protein-protein interactions and may mediate repression by the Mad-Max complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1274 codons.
• PP5: Variant 15-75372009-GACACGAT-G is Pathogenic according to our data. Variant chr15-75372009-GACACGAT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1708246.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3A	NM_001145358.2	c.3785_3791del	p.Tyr1262SerfsTer70	frameshift_variant	21/21	ENST00000394947.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3A	ENST00000394947.8	c.3785_3791del	p.Tyr1262SerfsTer70	frameshift_variant	21/21	1	NM_001145358.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

SIN3A-related intellectual disability syndrome due to a point mutation Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli

Oct 04, 2022

PVS1_moderate;PM2_supporting;PM6 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-75664350;