5-149597797-T-C

Variant names:

• chr5-149597797-T-C
• rs753993384
• NM_001001669.3:c.28T>C

Variant summary

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

The NM_001001669.3(ARHGEF37):​c.28T>C​(p.Ser10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. S10T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ARHGEF37 NM_001001669.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674
• Publications: 0 publications found

Genes affected

ARHGEF37 (HGNC:34430): (Rho guanine nucleotide exchange factor 37) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06920171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF37	NM_001001669.3	c.28T>C	p.Ser10Pro	missense_variant	Exon 2 of 13	ENST00000333677.7	NP_001001669.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF37	ENST00000333677.7	c.28T>C	p.Ser10Pro	missense_variant	Exon 2 of 13	2	NM_001001669.3	ENSP00000328083.6
ARHGEF37	ENST00000505810.5	c.28T>C	p.Ser10Pro	missense_variant	Exon 2 of 3	5		ENSP00000425621.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418570 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 703204

African (AFR) AF: 0.00 AC: 0 AN: 31076

American (AMR) AF: 0.00 AC: 0 AN: 35058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24764

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37478

South Asian (SAS) AF: 0.00 AC: 0 AN: 80238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092594

Other (OTH) AF: 0.00 AC: 0 AN: 58658

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.8
DANN	Benign	0.97
DEOGEN2	Benign	0.0030	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M
PhyloP100		-0.67
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.046
Sift	Benign	0.22	T;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.0	.;B
Vest4		0.12
MutPred		0.21		Loss of phosphorylation at S10 (P = 0.0013);Loss of phosphorylation at S10 (P = 0.0013);
MVP		0.085
MPC		0.12
ClinPred		0.075	T
GERP RS		-2.7
Varity_R		0.087
gMVP		0.22
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753993384; hg19: chr5-148977360;