7-155802871-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000193.4(SHH):​c.*29A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.020 ( 0 hom., cov: 0)
Exomes 𝑓: 0.30 ( 5 hom. )
Failed GnomAD Quality Control

Consequence

SHH
NM_000193.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.79
Variant links:
Genes affected
SHH (HGNC:10848): (sonic hedgehog signaling molecule) This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 7-155802871-T-C is Benign according to our data. Variant chr7-155802871-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1200869.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SHHNM_000193.4 linkuse as main transcriptc.*29A>G 3_prime_UTR_variant 3/3 ENST00000297261.7 NP_000184.1 Q15465

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SHHENST00000297261 linkuse as main transcriptc.*29A>G 3_prime_UTR_variant 3/31 NM_000193.4 ENSP00000297261.2 Q15465
SHHENST00000430104.5 linkuse as main transcriptc.302-2626A>G intron_variant 1 ENSP00000396621.1 C9JC48
SHHENST00000435425.1 linkuse as main transcriptn.302-2274A>G intron_variant 1 ENSP00000413871.1 F8WEH4
SHHENST00000441114.5 linkuse as main transcriptn.302-2204A>G intron_variant 1 ENSP00000410546.1 F8WB84

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
895
AN:
44274
Hom.:
0
Cov.:
0
FAILED QC
Gnomad AFR
AF:
0.0203
Gnomad AMI
AF:
0.0139
Gnomad AMR
AF:
0.0139
Gnomad ASJ
AF:
0.0175
Gnomad EAS
AF:
0.0186
Gnomad SAS
AF:
0.0247
Gnomad FIN
AF:
0.0173
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0227
Gnomad OTH
AF:
0.0172
GnomAD3 exomes
AF:
0.0290
AC:
335
AN:
11538
Hom.:
0
AF XY:
0.0296
AC XY:
199
AN XY:
6732
show subpopulations
Gnomad AFR exome
AF:
0.00862
Gnomad AMR exome
AF:
0.115
Gnomad ASJ exome
AF:
0.0212
Gnomad EAS exome
AF:
0.0492
Gnomad SAS exome
AF:
0.0366
Gnomad FIN exome
AF:
0.0303
Gnomad NFE exome
AF:
0.0169
Gnomad OTH exome
AF:
0.0474
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.302
AC:
53314
AN:
176720
Hom.:
5
Cov.:
5
AF XY:
0.293
AC XY:
25921
AN XY:
88324
show subpopulations
Gnomad4 AFR exome
AF:
0.298
Gnomad4 AMR exome
AF:
0.171
Gnomad4 ASJ exome
AF:
0.177
Gnomad4 EAS exome
AF:
0.165
Gnomad4 SAS exome
AF:
0.269
Gnomad4 FIN exome
AF:
0.127
Gnomad4 NFE exome
AF:
0.328
Gnomad4 OTH exome
AF:
0.269
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0202
AC:
897
AN:
44324
Hom.:
0
Cov.:
0
AF XY:
0.0192
AC XY:
444
AN XY:
23182
show subpopulations
Gnomad4 AFR
AF:
0.0204
Gnomad4 AMR
AF:
0.0141
Gnomad4 ASJ
AF:
0.0175
Gnomad4 EAS
AF:
0.0187
Gnomad4 SAS
AF:
0.0240
Gnomad4 FIN
AF:
0.0173
Gnomad4 NFE
AF:
0.0227
Gnomad4 OTH
AF:
0.0171
Alfa
AF:
0.0590
Hom.:
0

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 23, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.4
DANN
Benign
0.57

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

LitVar

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

Other links and lift over

dbSNP: rs767315773; hg19: chr7-155595565; API