chr8-22554589-C-T

Variant names:

• chr8-22554589-C-T
• rs753866090
• NM_005775.5:c.83C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005775.5(SORBS3):​c.83C>T​(p.Ser28Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: SORBS3 NM_005775.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16994041).

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.83C>T	p.Ser28Phe	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.83C>T	p.Ser28Phe	missense	Exon 2 of 21	ENSP00000240123.7	O60504-1
	SORBS3	ENST00000897780.1		c.83C>T	p.Ser28Phe	missense	Exon 2 of 21	ENSP00000567839.1
	SORBS3	ENST00000897778.1		c.83C>T	p.Ser28Phe	missense	Exon 2 of 21	ENSP00000567837.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000603 AC: 15 AN: 248682 AF XY: 0.0000667

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000240 AC: 35 AN: 1460386 Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24 AN XY: 726544

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111918

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152246 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74378

African (AFR) AF: 0.0000723 AC: 3 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.5
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.022	D
Polyphen		0.61	P
Vest4		0.49
MutPred		0.19		Loss of disorder (P = 0.0262)
MVP		0.54
MPC		0.16
ClinPred		0.077	T
GERP RS		4.3
PromoterAI		0.034	Neutral
Varity_R		0.17
gMVP		0.27
Mutation Taster		=84/16	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: rs753866090; hg19: chr8-22412102;