chr16-67538738-G-T

Variant names:

• chr16-67538738-G-T
• rs755576251
• NM_024519.4:c.171G>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.171G>T​(p.Arg57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,148 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RIPOR1 NM_024519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.2207731).

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246066 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: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461148 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726898

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52802

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

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	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	0.22	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
Polyphen		0.36	B
Vest4		0.56
MutPred		0.33		Loss of MoRF binding (P = 0.0132)
MVP		0.093
MPC		0.89
ClinPred		0.91	D
GERP RS		1.0
Varity_R		0.59
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs755576251; hg19: chr16-67572641;