rs367666999

Variant names:

• chr5-149597788-G-A
• rs367666999
• NM_001001669.3:c.19G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-149597788-G-A
• chr5-149597788-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001669.3(ARHGEF37):​c.19G>A​(p.Asp7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,567,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: ARHGEF37 NM_001001669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03459686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF37	NM_001001669.3	c.19G>A	p.Asp7Asn	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.19G>A	p.Asp7Asn	missense_variant	Exon 2 of 13	2	NM_001001669.3	ENSP00000328083.6
ARHGEF37	ENST00000505810.5	c.19G>A	p.Asp7Asn	missense_variant	Exon 2 of 3	5		ENSP00000425621.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000102 AC: 22 AN: 215802 AF XY: 0.000110

Gnomad AFR exome AF: 0.0000728

Gnomad AMR exome AF: 0.000712

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000194

Gnomad OTH exome AF: 0.000200

GnomAD4 exome AF: 0.0000304 AC: 43 AN: 1415352 Hom.: 0 Cov.: 30 AF XY: 0.0000299 AC XY: 21 AN XY: 701302

African (AFR) AF: 0.000259 AC: 8 AN: 30882

American (AMR) AF: 0.000552 AC: 19 AN: 34412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24616

East Asian (EAS) AF: 0.00 AC: 0 AN: 37406

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.0000128 AC: 14 AN: 1091080

Other (OTH) AF: 0.0000171 AC: 1 AN: 58532

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74450

African (AFR) AF: 0.000505 AC: 21 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000110

ESP6500AA AF: 0.000249 AC: 1

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.000116 AC: 14

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>A (p.D7N) alteration is located in exon 2 (coding exon 1) of the ARHGEF37 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the aspartic acid (D) at amino acid position 7 to be replaced by an asparagine (N). 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	0.081
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0016	.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;M
PhyloP100		1.7
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.080
Sift	Benign	0.030	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.80	.;P
Vest4		0.30
MVP		0.095
MPC		0.17
ClinPred		0.026	T
GERP RS		3.9
Varity_R		0.068
gMVP		0.15
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs367666999; hg19: chr5-148977351;