1-182904427-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_030933.4(SHCBP1L):ā€‹c.1340T>Cā€‹(p.Val447Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 1,613,378 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.0065 ( 9 hom., cov: 32)
Exomes š‘“: 0.0070 ( 68 hom. )

Consequence

SHCBP1L
NM_030933.4 missense

Scores

1
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.66
Variant links:
Genes affected
SHCBP1L (HGNC:16788): (SHC binding and spindle associated 1 like) This gene encodes a Src homology 2 domain-binding protein 1-like protein. The encoded protein interacts with heat shock 70 kDa protein 2 and may be involved in maintaining spindle integrity during meiosis. This gene is located in region of chromoso0me 1 encompassing a prostate cancer susceptibility locus. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0073943734).
BP6
Variant 1-182904427-A-G is Benign according to our data. Variant chr1-182904427-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639621.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SHCBP1LNM_030933.4 linkuse as main transcriptc.1340T>C p.Val447Ala missense_variant 8/10 ENST00000367547.8 NP_112195.2
SHCBP1LNM_001345928.2 linkuse as main transcriptc.983T>C p.Val328Ala missense_variant 9/11 NP_001332857.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SHCBP1LENST00000367547.8 linkuse as main transcriptc.1340T>C p.Val447Ala missense_variant 8/101 NM_030933.4 ENSP00000356518 P1Q9BZQ2-3
SHCBP1LENST00000483655.5 linkuse as main transcriptn.1283T>C non_coding_transcript_exon_variant 9/111
SHCBP1LENST00000488956.5 linkuse as main transcriptn.1800T>C non_coding_transcript_exon_variant 7/92

Frequencies

GnomAD3 genomes
AF:
0.00654
AC:
993
AN:
151790
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00153
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00184
Gnomad ASJ
AF:
0.00260
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.0350
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00762
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.00671
AC:
1683
AN:
250682
Hom.:
12
AF XY:
0.00617
AC XY:
837
AN XY:
135696
show subpopulations
Gnomad AFR exome
AF:
0.00125
Gnomad AMR exome
AF:
0.00125
Gnomad ASJ exome
AF:
0.00506
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.0304
Gnomad NFE exome
AF:
0.00773
Gnomad OTH exome
AF:
0.00525
GnomAD4 exome
AF:
0.00703
AC:
10268
AN:
1461470
Hom.:
68
Cov.:
32
AF XY:
0.00672
AC XY:
4884
AN XY:
727016
show subpopulations
Gnomad4 AFR exome
AF:
0.00111
Gnomad4 AMR exome
AF:
0.00152
Gnomad4 ASJ exome
AF:
0.00517
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.0292
Gnomad4 NFE exome
AF:
0.00727
Gnomad4 OTH exome
AF:
0.00611
GnomAD4 genome
AF:
0.00654
AC:
993
AN:
151908
Hom.:
9
Cov.:
32
AF XY:
0.00738
AC XY:
548
AN XY:
74224
show subpopulations
Gnomad4 AFR
AF:
0.00152
Gnomad4 AMR
AF:
0.00184
Gnomad4 ASJ
AF:
0.00260
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.0350
Gnomad4 NFE
AF:
0.00762
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00651
Hom.:
6
Bravo
AF:
0.00416
TwinsUK
AF:
0.00755
AC:
28
ALSPAC
AF:
0.0104
AC:
40
ESP6500AA
AF:
0.00204
AC:
9
ESP6500EA
AF:
0.00756
AC:
65
ExAC
AF:
0.00623
AC:
756
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00682
EpiControl
AF:
0.00616

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 testingCeGaT Center for Human Genetics TuebingenApr 01, 2022SHCBP1L: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
18
DANN
Benign
0.97
Eigen
Benign
-0.088
Eigen_PC
Benign
0.038
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.55
T
MetaRNN
Benign
0.0074
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.82
D;D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.039
Sift
Benign
0.22
T
Sift4G
Uncertain
0.010
D
Vest4
0.11
MVP
0.14
MPC
0.20
ClinPred
0.018
T
GERP RS
4.4
Varity_R
0.11
gMVP
0.33

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: rs143434276; hg19: chr1-182873562; COSMIC: COSV62354690; API