1-17587636-C-A

Variant names:

• chr1-17587636-C-A
• rs1313565082
• NM_018125.4:c.214C>A

Variant summary

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

The NM_018125.4(ARHGEF10L):​c.214C>A​(p.Pro72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. P72S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARHGEF10L NM_018125.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 0 publications found

Genes affected

ARHGEF10L (HGNC:25540): (Rho guanine nucleotide exchange factor 10 like) This gene belongs to the RhoGEF subfamily of RhoGTPases. Members of this subfamily are activated by specific guanine nucleotide exchange factors (GEFs) and are involved in signal transduction. The encoded protein shows cytosolic distribution. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2016]

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=0.14726654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018125.4. 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
	ARHGEF10L	NM_018125.4	MANE Select	c.214C>A	p.Pro72Thr	missense	Exon 3 of 29	NP_060595.3
	ARHGEF10L	NM_001011722.2		c.214C>A	p.Pro72Thr	missense	Exon 2 of 27	NP_001011722.2	Q9HCE6-2
	ARHGEF10L	NM_001438939.1		c.214C>A	p.Pro72Thr	missense	Exon 3 of 27	NP_001425868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10L	ENST00000361221.8	TSL:1 MANE Select	c.214C>A	p.Pro72Thr	missense	Exon 3 of 29	ENSP00000355060.3	Q9HCE6-1
	ARHGEF10L	ENST00000375415.5	TSL:1	c.214C>A	p.Pro72Thr	missense	Exon 2 of 27	ENSP00000364564.1	Q9HCE6-2
	ARHGEF10L	ENST00000970707.1		c.214C>A	p.Pro72Thr	missense	Exon 3 of 29	ENSP00000640766.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458548 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725404

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 85960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110262

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.1
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.042
Sift	Uncertain	0.010	D
Sift4G	Benign	0.11	T
Polyphen		0.32	B
Vest4		0.44
MutPred		0.39		Gain of sheet (P = 0.0061)
MVP		0.50
MPC		0.078
ClinPred		0.46	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.27
Mutation Taster		=95/5	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: rs1313565082; hg19: chr1-17914131;