1-248811971-G-C

Variant names:

• chr1-248811971-G-C
• rs370746257
• NM_030645.3:c.1111C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030645.3(SH3BP5L):​c.1111C>G​(p.Arg371Gly) 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. 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. R371W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3BP5L NM_030645.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 2 publications found

Genes affected

SH3BP5L (HGNC:29360): (SH3 binding domain protein 5 like) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in intracellular signal transduction and negative regulation of protein tyrosine kinase activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06635347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP5L	NM_030645.3	c.1111C>G	p.Arg371Gly	missense_variant	Exon 7 of 7	ENST00000366472.6	NP_085148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP5L	ENST00000366472.6	c.1111C>G	p.Arg371Gly	missense_variant	Exon 7 of 7	1	NM_030645.3	ENSP00000355428.5
SH3BP5L	ENST00000475978.1	n.2603C>G		non_coding_transcript_exon_variant	Exon 9 of 9	2
SH3BP5L	ENST00000484202.2	n.1585C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.14
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Uncertain	0.029	D
Sift4G	Benign	0.24	T
Polyphen		0.011	B
Vest4		0.085
MutPred		0.17		Loss of MoRF binding (P = 0.0094);
MVP		0.14
MPC		0.61
ClinPred		0.094	T
GERP RS		1.1
Varity_R		0.072
gMVP		0.14
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs370746257; hg19: chr1-249106170;