rs527903933

Variant names:

• chr1-17607960-G-A
• NM_018125.4:c.592G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-17607960-G-A
• chr1-17607960-G-C
• chr1-17607960-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018125.4(ARHGEF10L):​c.592G>A​(p.Val198Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,322,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V198L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ARHGEF10L NM_018125.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24987713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10L	NM_018125.4	c.592G>A	p.Val198Met	missense_variant	Exon 7 of 29	ENST00000361221.8	NP_060595.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10L	ENST00000361221.8	c.592G>A	p.Val198Met	missense_variant	Exon 7 of 29	1	NM_018125.4	ENSP00000355060.3
ARHGEF10L	ENST00000375415.5	c.592G>A	p.Val198Met	missense_variant	Exon 6 of 27	1		ENSP00000364564.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1322900 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 647214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000368

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.11
Sift	Benign	0.043	D;T
Sift4G	Benign	0.14	T;T
Polyphen		0.66	P;P
Vest4		0.42
MutPred		0.17		Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);
MVP		0.54
MPC		0.14
ClinPred		0.69	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.15

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-17934455;