6-71887055-G-A

Variant names:

• chr6-71887055-G-A
• rs1335808918
• NM_014989.7:c.32G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014989.7(RIMS1):​c.32G>A​(p.Arg11His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIMS1 NM_014989.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.10
• Publications: 1 publications found

Genes affected

RIMS1 (HGNC:17282): (regulating synaptic membrane exocytosis 1) The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

RIMS1 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 7

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.346963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014989.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	NM_014989.7	MANE Select	c.32G>A	p.Arg11His	missense	Exon 1 of 34	NP_055804.2
	RIMS1	NM_001350413.1		c.32G>A	p.Arg11His	missense	Exon 1 of 4	NP_001337342.1
	RIMS1	NM_001350411.1		c.32G>A	p.Arg11His	missense	Exon 1 of 4	NP_001337340.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.32G>A	p.Arg11His	missense	Exon 1 of 34	ENSP00000428417.1	Q86UR5-1
	RIMS1	ENST00000264839.11	TSL:5	c.32G>A	p.Arg11His	missense	Exon 1 of 30	ENSP00000264839.7	Q86UR5-4
	RIMS1	ENST00000697193.1		c.32G>A	p.Arg11His	missense	Exon 1 of 29	ENSP00000513179.1	A0A8V8TKU9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.75	N
PhyloP100		5.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.046	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.37
MutPred		0.18		Loss of methylation at R11 (P = 0.0299)
MVP		0.70
MPC		1.6
ClinPred		0.95	D
GERP RS		4.6
PromoterAI		-0.0054	Neutral
Varity_R		0.18
gMVP		0.54
Mutation Taster		=71/29	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: rs1335808918; hg19: chr6-72596758;