6-148440226-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015278.5(SASH1):ā€‹c.328C>Gā€‹(p.Gln110Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00134 in 1,614,052 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.0071 ( 18 hom., cov: 31)
Exomes š‘“: 0.00074 ( 10 hom. )

Consequence

SASH1
NM_015278.5 missense

Scores

5
13

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.43
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008813471).
BP6
Variant 6-148440226-C-G is Benign according to our data. Variant chr6-148440226-C-G is described in ClinVar as [Benign]. Clinvar id is 716141.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00706 (1074/152194) while in subpopulation AFR AF= 0.0245 (1019/41532). AF 95% confidence interval is 0.0233. There are 18 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SASH1NM_015278.5 linkuse as main transcriptc.328C>G p.Gln110Glu missense_variant 3/20 ENST00000367467.8 NP_056093.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SASH1ENST00000367467.8 linkuse as main transcriptc.328C>G p.Gln110Glu missense_variant 3/201 NM_015278.5 ENSP00000356437 P1
SASH1ENST00000367469.5 linkuse as main transcriptn.246C>G non_coding_transcript_exon_variant 3/43

Frequencies

GnomAD3 genomes
AF:
0.00708
AC:
1076
AN:
152076
Hom.:
18
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0247
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00282
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:
0.0000588
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00183
AC:
461
AN:
251432
Hom.:
10
AF XY:
0.00132
AC XY:
179
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.0256
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.000742
AC:
1085
AN:
1461858
Hom.:
10
Cov.:
31
AF XY:
0.000667
AC XY:
485
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0260
Gnomad4 AMR exome
AF:
0.00130
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.00194
GnomAD4 genome
AF:
0.00706
AC:
1074
AN:
152194
Hom.:
18
Cov.:
31
AF XY:
0.00721
AC XY:
536
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.0245
Gnomad4 AMR
AF:
0.00282
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00122
Hom.:
1
Bravo
AF:
0.00817
ESP6500AA
AF:
0.0236
AC:
104
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00227
AC:
275
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Benign
0.88
DEOGEN2
Benign
0.014
T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.94
D
MetaRNN
Benign
0.0088
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.27
N
MutationTaster
Benign
0.98
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.37
N
REVEL
Benign
0.19
Sift
Benign
0.22
T
Sift4G
Benign
1.0
T
Polyphen
0.98
D
Vest4
0.72
MVP
0.59
MPC
0.21
ClinPred
0.033
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.085

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs34521137; hg19: chr6-148761362; API