8-144545566-C-T

Position:

• chr8-144545566-C-T

Variant summary

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

The NM_025251.3(ARHGAP39):​c.2204G>A​(p.Ser735Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGAP39 NM_025251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

Genes affected

ARHGAP39 (HGNC:29351): (Rho GTPase activating protein 39) Predicted to enable GTPase activator activity. Involved in postsynapse organization. Is active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11111039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP39	NM_025251.3	c.2204G>A	p.Ser735Asn	missense_variant	6/12	ENST00000377307.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP39	ENST00000377307.7	c.2204G>A	p.Ser735Asn	missense_variant	6/12	5	NM_025251.3
ARHGAP39	ENST00000276826.5	c.2204G>A	p.Ser735Asn	missense_variant	5/10	2		P1
ARHGAP39	ENST00000528810.1	n.99G>A		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.71	N;N
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.11
Sift	Benign	0.16	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.14	B;B
Vest4		0.12
MutPred		0.55		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.68
MPC		0.34
ClinPred		0.46	T
GERP RS		4.3
Varity_R		0.13
gMVP		0.48

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: chr8-145770950; COSMIC: COSV52774316;