16-67538738-G-C

Variant names:

• chr16-67538738-G-C
• NM_024519.4:c.171G>C
• RIPOR1 p.Arg57Ser

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.171G>C​(p.Arg57Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIPOR1 NM_024519.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• 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: 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=0.22795528).

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.171G>C	p.Arg57Ser	missense	Exon 3 of 22	NP_078795.2
	RIPOR1	NM_001193523.2		c.231G>C	p.Arg77Ser	missense	Exon 3 of 22	NP_001180452.1	Q6ZS17-4
	RIPOR1	NM_001410885.1		c.231G>C	p.Arg77Ser	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.171G>C	p.Arg57Ser	missense	Exon 3 of 22	ENSP00000042381.4	Q6ZS17-2
	RIPOR1	ENST00000422602.8	TSL:2	c.231G>C	p.Arg77Ser	missense	Exon 3 of 22	ENSP00000400099.2	Q6ZS17-4
	RIPOR1	ENST00000540839.7	TSL:5	c.231G>C	p.Arg77Ser	missense	Exon 4 of 23	ENSP00000443568.3	A0A0A0MTL6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.083
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Varity_R		0.59
gMVP		0.54

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-67572641;