chr19-35779086-A-G

Variant names:

• chr19-35779086-A-G
• rs373417733
• NM_001366178.1:c.463A>G

Variant summary

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

The NM_001366178.1(ARHGAP33):​c.463A>G​(p.Ser155Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,551,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: ARHGAP33 NM_001366178.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.65
• Publications: 1 publications found

Genes affected

ARHGAP33 (HGNC:23085): (Rho GTPase activating protein 33) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. Alternative splice variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

ARHGAP33 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366178.1. 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
	ARHGAP33	NM_001366178.1	MANE Select	c.463A>G	p.Ser155Gly	missense	Exon 6 of 21	NP_001353107.1	O14559-1
	ARHGAP33	NM_052948.4		c.463A>G	p.Ser155Gly	missense	Exon 6 of 21	NP_443180.2
	ARHGAP33	NM_001172630.2		c.55A>G	p.Ser19Gly	missense	Exon 5 of 21	NP_001166101.1	O14559-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP33	ENST00000007510.9	TSL:5 MANE Select	c.463A>G	p.Ser155Gly	missense	Exon 6 of 21	ENSP00000007510.6	O14559-1
	ARHGAP33	ENST00000221905.1	TSL:1	n.517A>G		non_coding_transcript_exon	Exon 5 of 6
	ARHGAP33	ENST00000314737.9	TSL:2	c.463A>G	p.Ser155Gly	missense	Exon 6 of 21	ENSP00000320038.4	O14559-11

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000184 AC: 29 AN: 157796 AF XY: 0.000205

Gnomad AFR exome AF: 0.000113

Gnomad AMR exome AF: 0.000404

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000294

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000390 AC: 546 AN: 1399390 Hom.: 0 Cov.: 33 AF XY: 0.000377 AC XY: 260 AN XY: 690270

African (AFR) AF: 0.0000633 AC: 2 AN: 31600

American (AMR) AF: 0.000420 AC: 15 AN: 35724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 35742

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5384

European-Non Finnish (NFE) AF: 0.000480 AC: 518 AN: 1079176

Other (OTH) AF: 0.000172 AC: 10 AN: 57998

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74360

African (AFR) AF: 0.000121 AC: 5 AN: 41450

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68036

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000444 Hom.: 0

Bravo AF: 0.000200

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000243 AC: 2

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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		8.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Benign	0.035	D
Sift4G	Uncertain	0.037	D
Polyphen		0.18	B
Vest4		0.32
MVP		0.53
MPC		0.74
ClinPred		0.096	T
GERP RS		5.5
gMVP		0.53
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.41		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373417733; hg19: chr19-36269988;