chr16-67538746-C-T

Variant names:

• chr16-67538746-C-T
• rs374261841
• NM_024519.4:c.179C>T

Variant summary

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

The NM_024519.4(RIPOR1):​c.179C>T​(p.Ser60Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,613,364 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (1 hom.)
• Consequence: RIPOR1 NM_024519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55
• Publications: 2 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: 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=0.23961622).

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.179C>T	p.Ser60Phe	missense	Exon 3 of 22	NP_078795.2
	RIPOR1	NM_001193523.2		c.239C>T	p.Ser80Phe	missense	Exon 3 of 22	NP_001180452.1	Q6ZS17-4
	RIPOR1	NM_001410885.1		c.239C>T	p.Ser80Phe	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.179C>T	p.Ser60Phe	missense	Exon 3 of 22	ENSP00000042381.4	Q6ZS17-2
	RIPOR1	ENST00000422602.8	TSL:2	c.239C>T	p.Ser80Phe	missense	Exon 3 of 22	ENSP00000400099.2	Q6ZS17-4
	RIPOR1	ENST00000540839.7	TSL:5	c.239C>T	p.Ser80Phe	missense	Exon 4 of 23	ENSP00000443568.3	A0A0A0MTL6

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152224 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: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 245856 AF XY: 0.00000744

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1461140 Hom.: 1 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 726896

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111940

Other (OTH) AF: 0.000530 AC: 32 AN: 60386

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

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

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.00173 AC: 6 AN: 3478

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	0.24
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.80	P
Vest4		0.46
MutPred		0.37		Loss of disorder (P = 0.0263)
MVP		0.19
MPC		1.2
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.40
gMVP		0.45
Mutation Taster		=76/24	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: rs374261841; hg19: chr16-67572649;