chr15-30635547-G-T

Variant names:

• chr15-30635547-G-T
• rs2060274635
• ENST00000428041.4:c.721G>T

Variant summary

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

The ENST00000428041.4(ARHGAP11B):​c.721G>T​(p.Val241Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ARHGAP11B ENST00000428041.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

ARHGAP11B (HGNC:15782): (Rho GTPase activating protein 11B) Predicted to enable GTPase activator activity. Involved in cerebral cortex development and negative regulation of mitochondrial membrane permeability. Acts upstream of with a positive effect on glutamine catabolic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284906 (HGNC:):

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=0.07851517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP11B	NM_001039841.3	c.721G>T	p.Val241Leu	missense_variant	Exon 6 of 7		NP_001034930.1
ARHGAP11B	NR_148423.2	n.1414G>T		non_coding_transcript_exon_variant	Exon 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284906	ENST00000685924.1	c.721G>T	p.Val241Leu	missense_variant	Exon 6 of 15			ENSP00000510601.1
ARHGAP11B	ENST00000697964.2	c.721G>T	p.Val241Leu	missense_variant	Exon 6 of 7			ENSP00000513489.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.721G>T (p.V241L) alteration is located in exon 6 (coding exon 6) of the ARHGAP11B gene. This alteration results from a G to T substitution at nucleotide position 721, causing the valine (V) at amino acid position 241 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.23
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.28	T;.
M_CAP	Benign	0.00086	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.75	N;.
PhyloP100		2.2
PROVEAN	Benign	-0.38	N;.
REVEL	Benign	0.063
Sift	Benign	0.81	T;.
Polyphen		0.0040	B;.
Vest4		0.15
MutPred		0.55		Loss of catalytic residue at V241 (P = 0.0997);Loss of catalytic residue at V241 (P = 0.0997);
MVP		0.055
MPC		0.45
ClinPred		0.037	T
GERP RS		1.5
Varity_R		0.076
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2060274635; hg19: chr15-30927750;