dbSNP rs193921086: SHCBP1L:p.Thr294Ile (chr1-182939371-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030933.4(SHCBP1L):c.881C>T(p.Thr294Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T294K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SHCBP1L
NM_030933.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19598454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHCBP1L	NM_030933.4 link	c.881C>T	p.Thr294Ile	missense_variant	Exon 5 of 10	ENST00000367547.8	NP_112195.2	Q9BZQ2-3
SHCBP1L	NM_001345928.2 link	c.524C>T	p.Thr175Ile	missense_variant	Exon 6 of 11		NP_001332857.1	Q9BZQ2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SHCBP1L	ENST00000367547.8 link	c.881C>T	p.Thr294Ile	missense_variant	Exon 5 of 10	1	NM_030933.4	ENSP00000356518.3	Q9BZQ2-3
SHCBP1L	ENST00000483655.5 link	n.824C>T		non_coding_transcript_exon_variant	Exon 6 of 11	1
SHCBP1L	ENST00000488956.5 link	n.1341C>T		non_coding_transcript_exon_variant	Exon 4 of 9	2
SHCBP1L	ENST00000467208.5 link	n.*103C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111896

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

0.0041

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.10

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.69

M_CAP

Benign

0.024

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.85

PhyloP100

2.4

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.8

REVEL

Benign

0.056

Sift

Benign

0.53

Sift4G

Benign

0.20

Vest4

0.33

MVP

0.43

MPC

0.26

ClinPred

0.64

GERP RS

5.0

Varity_R

0.12

gMVP

0.46

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over