chr6-148343106-T-TGAGCCCGAGCCC

Variant names:

• chr6-148343106-T-TGAGCCCGAGCCC
• rs76317765
• NM_015278.5:c.45_56dupCGAGCCCGAGCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015278.5(SASH1):​c.45_56dupCGAGCCCGAGCC​(p.Pro19_Glu20insGluProGluPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000432 in 1,573,634 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 0.000073 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: SASH1 NM_015278.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

Genes affected

SASH1 (HGNC:19182): (SAM and SH3 domain containing 1) This gene encodes a scaffold protein involved in the TLR4 signaling pathway that may stimulate cytokine production and endothelial cell migration in response to invading pathogens. The encoded protein has also been described as a potential tumor suppressor that may negatively regulate proliferation, apoptosis, and invasion of cancer cells, and reduced expression of this gene has been observed in multiple human cancers. Mutations in this gene may be associated with abnormal skin pigmentation in human patients. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
SASH1	NM_015278.5	c.45_56dupCGAGCCCGAGCC	p.Pro19_Glu20insGluProGluPro	disruptive_inframe_insertion	Exon 1 of 20	ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.45_56dupCGAGCCCGAGCC	p.Pro19_Glu20insGluProGluPro	disruptive_inframe_insertion	Exon 1 of 20	1	NM_015278.5	ENSP00000356437.3
SASH1	ENST00000367469.5	n.75-47022_75-47011dupCGAGCCCGAGCC		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0000728 AC: 11 AN: 151028 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000484

GnomAD3 exomes AF: 0.0000466 AC: 9 AN: 193108 Hom.: 0 AF XY: 0.0000466 AC XY: 5 AN XY: 107234

Gnomad AFR exome AF: 0.0000918

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000363

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000810

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000401 AC: 57 AN: 1422494 Hom.: 0 Cov.: 31 AF XY: 0.0000425 AC XY: 30 AN XY: 706144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000598

Gnomad4 FIN exome AF: 0.0000819

Gnomad4 NFE exome AF: 0.0000400

Gnomad4 OTH exome AF: 0.0000675

GnomAD4 genome AF: 0.0000728 AC: 11 AN: 151140 Hom.: 0 Cov.: 30 AF XY: 0.000122 AC XY: 9 AN XY: 73808

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76317765; hg19: chr6-148664242;