2-38919458-C-T

Variant names:

• chr2-38919458-C-T
• rs750138898
• NM_001145451.5:c.11C>T

Variant summary

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

The NM_001145451.5(ARHGEF33):​c.11C>T​(p.Thr4Ile) 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. T4S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGEF33 NM_001145451.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 1 publications found

Genes affected

ARHGEF33 (HGNC:37252): (Rho guanine nucleotide exchange factor 33) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000310583 (HGNC:):

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=0.06801036).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145451.5. 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
	ARHGEF33	NM_001145451.5	MANE Select	c.11C>T	p.Thr4Ile	missense	Exon 3 of 18	NP_001138923.2	A8MVX0-2
	ARHGEF33	NM_001367623.3		c.11C>T	p.Thr4Ile	missense	Exon 3 of 19	NP_001354552.1	A8MVX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF33	ENST00000409978.7	TSL:5 MANE Select	c.11C>T	p.Thr4Ile	missense	Exon 3 of 18	ENSP00000387020.1	A8MVX0-2
	ENSG00000310583	ENST00000441049.6	TSL:5	n.*204C>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000401340.2
	ENSG00000310583	ENST00000441049.6	TSL:5	n.*204C>T		3_prime_UTR	Exon 7 of 9	ENSP00000401340.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.97
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.13
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.055
Sift	Benign	0.042	D
Sift4G	Benign	0.18	T
Vest4		0.14
MutPred		0.11		Loss of phosphorylation at T4 (P = 0.0199)
MVP		0.15
ClinPred		0.14	T
GERP RS		2.3
PromoterAI		-0.027	Neutral
gMVP		0.56
Mutation Taster		=93/7	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: rs750138898; hg19: chr2-39146599; COSMIC: COSV104706116;