8-22554551-C-A

Variant names:

• chr8-22554551-C-A
• rs369770694
• NM_005775.5:c.45C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005775.5(SORBS3):​c.45C>A​(p.Asp15Glu) 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. 14/22 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. D15N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SORBS3 NM_005775.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 0 publications found

Genes affected

SORBS3 (HGNC:30907): (sorbin and SH3 domain containing 3) This gene encodes an SH3 domain-containing adaptor protein. The presence of SH3 domains play a role in this protein's ability to bind other cytoplasmic molecules and contribute to cystoskeletal organization, cell adhesion and migration, signaling, and gene expression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

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=0.16385159).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005775.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS3	NM_005775.5	MANE Select	c.45C>A	p.Asp15Glu	missense	Exon 2 of 21	NP_005766.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS3	ENST00000240123.12	TSL:1 MANE Select	c.45C>A	p.Asp15Glu	missense	Exon 2 of 21	ENSP00000240123.7	O60504-1
	SORBS3	ENST00000897780.1		c.45C>A	p.Asp15Glu	missense	Exon 2 of 21	ENSP00000567839.1
	SORBS3	ENST00000897778.1		c.45C>A	p.Asp15Glu	missense	Exon 2 of 21	ENSP00000567837.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.91
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-2.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.091
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.62	P
Vest4		0.30
MutPred		0.28		Loss of stability (P = 0.1053)
MVP		0.39
MPC		0.23
ClinPred		0.59	D
GERP RS		-4.6
PromoterAI		-0.0040	Neutral
Varity_R		0.17
gMVP		0.37
Mutation Taster		=86/14	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: rs369770694; hg19: chr8-22412064;