rs193921086

Positions:

• chr1-182939371-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.881C>A​(p.Thr294Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SHCBP1L NM_030933.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.38

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=0.4186258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHCBP1L	NM_030933.4	c.881C>A	p.Thr294Lys	missense_variant	5/10	ENST00000367547.8	NP_112195.2
SHCBP1L	NM_001345928.2	c.524C>A	p.Thr175Lys	missense_variant	6/11		NP_001332857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHCBP1L	ENST00000367547.8	c.881C>A	p.Thr294Lys	missense_variant	5/10	1	NM_030933.4	ENSP00000356518	P1
SHCBP1L	ENST00000483655.5	n.824C>A		non_coding_transcript_exon_variant	6/11	1
SHCBP1L	ENST00000488956.5	n.1341C>A		non_coding_transcript_exon_variant	4/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251020 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461592 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.97
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	0.92	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.16
Sift	Benign	0.64	T
Sift4G	Uncertain	0.017	D
Vest4		0.59
MVP		0.52
MPC		0.61
ClinPred		0.58	D
GERP RS		5.0
Varity_R		0.090
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

LitVar

Other links and lift over

dbSNP: rs193921086; hg19: chr1-182908506; COSMIC: COSV62353340; COSMIC: COSV62353340;