6-148343106-T-TGAGCCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_015278.5(SASH1):c.51_56dup(p.Glu22_Pro23dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,573,028 control chromosomes in the GnomAD database, including 16,085 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1053 hom., cov: 30)
  • Exomes 𝑓: 0.14 (15032 hom.)
• Consequence: SASH1 NM_015278.5 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 6-148343106-T-TGAGCCC is Benign according to our data. Variant chr6-148343106-T-TGAGCCC is described in ClinVar as [Benign]. Clinvar id is 1290003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5	c.51_56dup	p.Glu22_Pro23dup	inframe_insertion	1/20	ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8	c.51_56dup	p.Glu22_Pro23dup	inframe_insertion	1/20	1	NM_015278.5	P1
SASH1	ENST00000367469.5	n.75-47016_75-47011dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16078 AN: 151000 Hom.: 1057 Cov.: 30

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.105 AC: 20233 AN: 193108 Hom.: 1265 AF XY: 0.106 AC XY: 11333 AN XY: 107234

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.0677

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.0468

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.140 AC: 199153 AN: 1421916 Hom.: 15032 Cov.: 31 AF XY: 0.137 AC XY: 97007 AN XY: 705828

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.0714

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0523

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.106 AC: 16067 AN: 151112 Hom.: 1053 Cov.: 30 AF XY: 0.105 AC XY: 7727 AN XY: 73794

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0548

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0336 Hom.: 14

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dyschromatosis universalis hereditaria 1;C5193062:Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 20, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

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;