19-38876471-T-G

Variant names:

• chr19-38876471-T-G
• rs1001413
• NM_001195833.2:c.70A>C

Variant summary

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

The ENST00000591812.2(RINL):​c.70A>C​(p.Asn24His) 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. 12/17 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. N24S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RINL ENST00000591812.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 34 publications found

Genes affected

RINL (HGNC:24795): (Ras and Rab interactor like) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in endocytosis. Predicted to be located in actin cytoskeleton and ruffle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269050 (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=0.15108702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000591812.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINL	NM_001195833.2	MANE Select	c.70A>C	p.Asn24His	missense	Exon 3 of 12	NP_001182762.1
	RINL	NM_198445.4		c.-273A>C		5_prime_UTR	Exon 3 of 12	NP_940847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINL	ENST00000591812.2	TSL:2 MANE Select	c.70A>C	p.Asn24His	missense	Exon 3 of 12	ENSP00000467107.1
	RINL	ENST00000589111.5	TSL:2	n.135A>C		non_coding_transcript_exon	Exon 3 of 9
	RINL	ENST00000598048.1	TSL:4	n.353A>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.0020	T
FATHMM_MKL	Benign	0.058	N
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.15	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.17
PrimateAI	Benign	0.34	T
Sift4G	Uncertain	0.021	D
Vest4		0.079
MVP		0.73
MPC		0.42
GERP RS		-0.17
PromoterAI		-0.052	Neutral
Varity_R		0.036
gMVP		0.42
Mutation Taster		=300/0	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: rs1001413; hg19: chr19-39367111;