8-22554585-G-A

Position:

• chr8-22554585-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005775.5(SORBS3):​c.79G>A​(p.Gly27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,466 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SORBS3 NM_005775.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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]

SORBS3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS3	NM_005775.5	c.79G>A	p.Gly27Arg	missense_variant	2/21	ENST00000240123.12	NP_005766.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS3	ENST00000240123.12	c.79G>A	p.Gly27Arg	missense_variant	2/21	1	NM_005775.5	ENSP00000240123.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460466 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726570

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 13, 2024

The c.79G>A (p.G27R) alteration is located in exon 2 (coding exon 1) of the SORBS3 gene. This alteration results from a G to A substitution at nucleotide position 79, causing the glycine (G) at amino acid position 27 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.013	D
Sift4G	Benign	0.32	T
Polyphen		0.77	P
Vest4		0.61
MutPred		0.40		Gain of MoRF binding (P = 0.003);
MVP		0.55
MPC		0.44
ClinPred		0.44	T
GERP RS		3.5
Varity_R		0.082
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: 1

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: chr8-22412098;