Variant 7-75073709-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030798.5(RCC1L):c.29C>T(p.Ala10Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RCC1L
NM_030798.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.581

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0815793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RCC1L	NM_030798.5 linkuse as main transcript	c.29C>T	p.Ala10Val	missense_variant	1/11	ENST00000610322.5	NP_110425.2
RCC1L	NM_148842.3 linkuse as main transcript	c.29C>T	p.Ala10Val	missense_variant	1/11		NP_683682.1
RCC1L	NM_001281441.2 linkuse as main transcript	c.29C>T	p.Ala10Val	missense_variant	1/9		NP_001268370.1
RCC1L	NM_001363447.2 linkuse as main transcript	c.-605C>T		5_prime_UTR_variant	1/11		NP_001350376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCC1L	ENST00000610322.5 linkuse as main transcript	c.29C>T	p.Ala10Val	missense_variant	1/11	1	NM_030798.5	ENSP00000480364	P1	Q96I51-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.40e-7

AC:

AN:

1350758

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

666080

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 16, 2021

The c.29C>T (p.A10V) alteration is located in exon 1 (coding exon 1) of the RCC1L gene. This alteration results from a C to T substitution at nucleotide position 29, causing the alanine (A) at amino acid position 10 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.74

Sift4G

Benign

0.37

T;T;T

Vest4

0.091

MutPred

0.39

Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);

MVP

0.040

ClinPred

0.17

GERP RS

1.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.2

gMVP

0.51

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over