Variant chr6-148343106-T-TGAGCCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.48

Variant links:

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]

SASH1 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	c.51_56dup	p.Glu22_Pro23dup	inframe_insertion	1/20	1	NM_015278.5	P1
SASH1	ENST00000367469.5 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.137

AC XY:

97007

AN XY:

705828

show subpopulations

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.:

AF XY:

0.105

AC XY:

7727

AN XY:

73794

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over