chr5-149621988-A-T

Variant names:

• chr5-149621988-A-T
• NM_001001669.3:c.1261A>T
• ARHGEF37 p.Met421Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001669.3(ARHGEF37):​c.1261A>T​(p.Met421Leu) 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. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGEF37 NM_001001669.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03268403).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001669.3. 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
	ARHGEF37	NM_001001669.3	MANE Select	c.1261A>T	p.Met421Leu	missense	Exon 9 of 13	NP_001001669.2	A1IGU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF37	ENST00000333677.7	TSL:2 MANE Select	c.1261A>T	p.Met421Leu	missense	Exon 9 of 13	ENSP00000328083.6	A1IGU5
	ARHGEF37	ENST00000857359.1		c.1261A>T	p.Met421Leu	missense	Exon 10 of 14	ENSP00000527418.1
	ARHGEF37	ENST00000941574.1		c.1261A>T	p.Met421Leu	missense	Exon 10 of 14	ENSP00000611633.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.6
DANN	Benign	0.61
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-3.1	N
PhyloP100		0.14
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.78	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.11
gMVP		0.17
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-149001551;