1-182900020-G-T

Position:

• chr1-182900020-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030933.4(SHCBP1L):​c.1925C>A​(p.Ala642Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHCBP1L NM_030933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38104776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHCBP1L	NM_030933.4	c.1925C>A	p.Ala642Glu	missense_variant	10/10	ENST00000367547.8	NP_112195.2
SHCBP1L	NM_001345928.2	c.1568C>A	p.Ala523Glu	missense_variant	11/11		NP_001332857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHCBP1L	ENST00000367547.8	c.1925C>A	p.Ala642Glu	missense_variant	10/10	1	NM_030933.4	ENSP00000356518.3
SHCBP1L	ENST00000483655.5	n.1868C>A		non_coding_transcript_exon_variant	11/11	1
SHCBP1L	ENST00000488956.5	n.2385C>A		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.1925C>A (p.A642E) alteration is located in exon 10 (coding exon 10) of the SHCBP1L gene. This alteration results from a C to A substitution at nucleotide position 1925, causing the alanine (A) at amino acid position 642 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.049
Eigen_PC	Benign	0.024
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.16
Sift	Benign	0.083	T
Sift4G	Benign	0.18	T
Vest4		0.63
MVP		0.22
MPC		0.49
ClinPred		0.85	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-182869155;