16-46581926-C-T

Variant names:

• chr16-46581926-C-T
• NM_024745.5:c.1822G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024745.5(SHCBP1):​c.1822G>A​(p.Val608Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHCBP1 NM_024745.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.382

Genes affected

SHCBP1 (HGNC:29547): (SHC binding and spindle associated 1) Predicted to enable SH2 domain binding activity. Predicted to be involved in fibroblast growth factor receptor signaling pathway and regulation of neural precursor cell proliferation. Predicted to be located in cytoplasm; midbody; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035481572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHCBP1	NM_024745.5	c.1822G>A	p.Val608Ile	missense_variant	Exon 13 of 13	ENST00000303383.8	NP_079021.4
SHCBP1	NM_001324318.2	c.1708G>A	p.Val570Ile	missense_variant	Exon 13 of 13		NP_001311247.1
SHCBP1	NM_001324319.2	c.1588G>A	p.Val530Ile	missense_variant	Exon 12 of 12		NP_001311248.1
SHCBP1	NR_136738.2	n.1919G>A		non_coding_transcript_exon_variant	Exon 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHCBP1	ENST00000303383.8	c.1822G>A	p.Val608Ile	missense_variant	Exon 13 of 13	1	NM_024745.5	ENSP00000306473.3
SHCBP1	ENST00000567698.1	n.522G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1822G>A (p.V608I) alteration is located in exon 13 (coding exon 13) of the SHCBP1 gene. This alteration results from a G to A substitution at nucleotide position 1822, causing the valine (V) at amino acid position 608 to be replaced by an isoleucine (I). 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	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.056
Sift	Benign	0.32	T
Sift4G	Benign	0.47	T
Polyphen		0.091	B
Vest4		0.021
MutPred		0.17		Gain of helix (P = 0.1736);
MVP		0.18
MPC		0.20
ClinPred		0.089	T
GERP RS		2.9
Varity_R		0.026
gMVP		0.16

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: chr16-46615838;