Variant chr1-182900177-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030933.4(SHCBP1L):c.1768T>C(p.Tyr590His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,610,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

SHCBP1L
NM_030933.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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]

SHCBP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHCBP1L	NM_030933.4 link	c.1768T>C	p.Tyr590His	missense_variant	10/10	ENST00000367547.8	NP_112195.2	Q9BZQ2-3
SHCBP1L	NM_001345928.2 link	c.1411T>C	p.Tyr471His	missense_variant	11/11		NP_001332857.1	Q9BZQ2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SHCBP1L	ENST00000367547.8 link	c.1768T>C	p.Tyr590His	missense_variant	10/10	1	NM_030933.4	ENSP00000356518.3	Q9BZQ2-3
SHCBP1L	ENST00000483655.5 link	n.1711T>C		non_coding_transcript_exon_variant	11/11	1
SHCBP1L	ENST00000488956.5 link	n.2228T>C		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000177

AC:

AN:

248226

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

134288

show subpopulations

Gnomad AFR exome

AF:

0.0000630

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000565

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000262

AC:

382

AN:

1458406

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

196

AN XY:

725382

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000503

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000286

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000131

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000206

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000173

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.1768T>C (p.Y590H) alteration is located in exon 10 (coding exon 10) of the SHCBP1L gene. This alteration results from a T to C substitution at nucleotide position 1768, causing the tyrosine (Y) at amino acid position 590 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

0.39

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.61

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Vest4

0.83

MVP

0.50

MPC

0.78

ClinPred

0.27

GERP RS

5.5

Varity_R

0.51

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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