16-67538701-C-T

Variant names:

• chr16-67538701-C-T
• rs200677001
• NM_024519.4:c.134C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024519.4(RIPOR1):​c.134C>T​(p.Pro45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,613,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: RIPOR1 NM_024519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85
• Publications: 0 publications found

Genes affected

RIPOR1 (HGNC:25836): (RHO family interacting cell polarization regulator 1) Enables 14-3-3 protein binding activity. Involved in several processes, including establishment of Golgi localization; negative regulation of Rho guanyl-nucleotide exchange factor activity; and negative regulation of Rho protein signal transduction. Located in Golgi apparatus; cell leading edge; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261396 (HGNC:):

CTCF-DT (HGNC:55409): (CTCF divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02505377).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024519.4. 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
	RIPOR1	NM_024519.4	MANE Select	c.134C>T	p.Pro45Leu	missense	Exon 3 of 22	NP_078795.2
	RIPOR1	NM_001193523.2		c.194C>T	p.Pro65Leu	missense	Exon 3 of 22	NP_001180452.1	Q6ZS17-4
	RIPOR1	NM_001410885.1		c.194C>T	p.Pro65Leu	missense	Exon 3 of 22	NP_001397814.1	A0A0A0MTL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPOR1	ENST00000042381.9	TSL:5 MANE Select	c.134C>T	p.Pro45Leu	missense	Exon 3 of 22	ENSP00000042381.4	Q6ZS17-2
	RIPOR1	ENST00000422602.8	TSL:2	c.194C>T	p.Pro65Leu	missense	Exon 3 of 22	ENSP00000400099.2	Q6ZS17-4
	RIPOR1	ENST00000540839.7	TSL:5	c.194C>T	p.Pro65Leu	missense	Exon 4 of 23	ENSP00000443568.3	A0A0A0MTL6

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000183 AC: 45 AN: 245822 AF XY: 0.000179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000695

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000209 AC: 306 AN: 1460960 Hom.: 0 Cov.: 32 AF XY: 0.000223 AC XY: 162 AN XY: 726808

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00100 AC: 53 AN: 52740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000213 AC: 237 AN: 1111862

Other (OTH) AF: 0.000265 AC: 16 AN: 60380

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000626 Hom.: 0

Bravo AF: 0.000136

ExAC AF: 0.000215 AC: 26

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.075
Sift	Benign	0.25	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.33
MVP		0.093
MPC		0.61
ClinPred		0.17	T
GERP RS		5.3
Varity_R		0.060
gMVP		0.19
Mutation Taster		=96/4	polymorphism

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: rs200677001; hg19: chr16-67572604;