Variant 7-75066792-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000610322.5(RCC1L):c.455C>T(p.Thr152Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,602,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 1 hom. )

Consequence

RCC1L
ENST00000610322.5 missense, splice_region

Scores

Splicing: ADA: 0.0001363

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00800

Variant links:

Genes affected

RCC1L (HGNC:14948): (RCC1 like) This gene encodes a protein containing regulator of chromosome condensation 1-like repeats. The encoded protein may function as a guanine nucleotide exchange factor. This gene is located in a region of chromosome 7 that is deleted in Williams-Beuren syndrome, a multisystem developmental disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RCC1L links:

RCC1L (HGNC:):

RCC1L links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012474507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCC1L	NM_030798.5 linkuse as main transcript	c.455C>T	p.Thr152Met	missense_variant, splice_region_variant	3/11	ENST00000610322.5	NP_110425.2	Q96I51-1
RCC1L	NM_148842.3 linkuse as main transcript	c.455C>T	p.Thr152Met	missense_variant, splice_region_variant	3/11		NP_683682.1	Q96I51-3
RCC1L	NM_001281441.2 linkuse as main transcript	c.455C>T	p.Thr152Met	missense_variant, splice_region_variant	3/9		NP_001268370.1	Q96I51-2
RCC1L	NM_001363447.2 linkuse as main transcript	c.56C>T	p.Thr19Met	missense_variant, splice_region_variant	3/11		NP_001350376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCC1L	ENST00000610322.5 linkuse as main transcript	c.455C>T	p.Thr152Met	missense_variant, splice_region_variant	3/11	1	NM_030798.5	ENSP00000480364.1		Q96I51-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000238

AC:

AN:

239394

Hom.:

AF XY:

0.000269

AC XY:

AN XY:

129966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000628

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00153

Gnomad SAS exome

AF:

0.000346

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000986

AC:

143

AN:

1449950

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

721144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000507

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00122

Gnomad4 SAS exome

AF:

0.000697

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000151

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000425

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.455C>T (p.T152M) alteration is located in exon 3 (coding exon 3) of the RCC1L gene. This alteration results from a C to T substitution at nucleotide position 455, causing the threonine (T) at amino acid position 152 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.1

DANN

Benign

0.81

DEOGEN2

Benign

0.023

.;.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.48

.;.;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.78

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.38

Sift4G

Benign

0.23

T;T;T;.

Vest4

0.12

MVP

0.067

ClinPred

0.0081

GERP RS

-6.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0060

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over