rs1394679827

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015278.5(SASH1):c.103G>C(p.Ala35Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,600,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SASH1
NM_015278.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.740

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

dyschromatosis universalis hereditaria 1
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics
familial generalized lentiginosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

SASH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14183602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015278.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SASH1	NM_015278.5	MANE Select	c.103G>C	p.Ala35Pro	missense	Exon 1 of 20	NP_056093.3
SASH1	NM_001346506.2		c.-335G>C		5_prime_UTR	Exon 1 of 21	NP_001333435.1
SASH1	NM_001346505.2		c.22-46964G>C		intron	N/A	NP_001333434.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SASH1	ENST00000367467.8	TSL:1 MANE Select	c.103G>C	p.Ala35Pro	missense	Exon 1 of 20	ENSP00000356437.3	O94885
SASH1	ENST00000946242.1		c.103G>C	p.Ala35Pro	missense	Exon 1 of 21	ENSP00000616301.1
SASH1	ENST00000946243.1		c.103G>C	p.Ala35Pro	missense	Exon 1 of 21	ENSP00000616302.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1448142

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.00

AC:

AN:

86068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1111264

Other (OTH)

AF:

0.0000166

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.013

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.44

M_CAP

Benign

0.066

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.97

PhyloP100

0.74

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.1

REVEL

Benign

0.10

Sift

Uncertain

0.010

Sift4G

Benign

0.23

Polyphen

0.84

Vest4

0.18

MutPred

0.14

Gain of glycosylation at A35 (P = 0.0028)

MVP

0.45

MPC

0.19

ClinPred

0.13

GERP RS

1.5

PromoterAI

0.028

Neutral

(source)

Varity_R

0.21

gMVP

0.23

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over