Variant 1-182900135-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_030933.4(SHCBP1L):c.1810G>A(p.Val604Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,612,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SHCBP1L
NM_030933.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.110

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041272044).

BP6

Variant 1-182900135-C-T is Benign according to our data. Variant chr1-182900135-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2358091.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHCBP1L	NM_030933.4 linkuse as main transcript	c.1810G>A	p.Val604Ile	missense_variant	10/10	ENST00000367547.8	NP_112195.2
SHCBP1L	NM_001345928.2 linkuse as main transcript	c.1453G>A	p.Val485Ile	missense_variant	11/11		NP_001332857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHCBP1L	ENST00000367547.8 linkuse as main transcript	c.1810G>A	p.Val604Ile	missense_variant	10/10	1	NM_030933.4	ENSP00000356518	P1	Q9BZQ2-3
SHCBP1L	ENST00000483655.5 linkuse as main transcript	n.1753G>A		non_coding_transcript_exon_variant	11/11	1
SHCBP1L	ENST00000488956.5 linkuse as main transcript	n.2270G>A		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000403

AC:

AN:

248276

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134248

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1460010

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

726262

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000243

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000845

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.69

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.55

M_CAP

Benign

0.0053

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.19

REVEL

Benign

0.015

Sift

Benign

0.29

Sift4G

Benign

0.40

Vest4

0.084

MVP

0.040

MPC

0.14

ClinPred

0.014

GERP RS

1.8

Varity_R

0.032

gMVP

0.30

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.

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