rs142588540

Variant names:

• chr19-48720907-T-A
• NM_017805.3:c.2783A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48720907-T-A
• chr19-48720907-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017805.3(RASIP1):​c.2783A>T​(p.Asp928Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D928G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RASIP1 NM_017805.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08

Genes affected

RASIP1 (HGNC:24716): (Ras interacting protein 1) Enables GTPase binding activity and protein homodimerization activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of Rho-dependent protein serine/threonine kinase activity; and positive regulation of integrin activation. Located in cell-cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASIP1	NM_017805.3	c.2783A>T	p.Asp928Val	missense_variant	Exon 12 of 12	ENST00000222145.9	NP_060275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASIP1	ENST00000222145.9	c.2783A>T	p.Asp928Val	missense_variant	Exon 12 of 12	1	NM_017805.3	ENSP00000222145.3
RASIP1	ENST00000601530.1	n.1277A>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727106

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Benign	0.17
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.046	D
Polyphen		0.84	P
Vest4		0.81
MutPred		0.52		Loss of disorder (P = 0.0161);
MVP		0.38
MPC		1.9
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.51
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-49224164;