Variant 1-167685425-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052862.4(RCSD1):c.113C>T(p.Pro38Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,442 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: 0.0000034 ( 0 hom. )

Consequence

RCSD1
NM_052862.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

Variant links:

Genes affected

RCSD1 (HGNC:28310): (RCSD domain containing 1) Enables actin filament binding activity. Involved in cellular hyperosmotic response. Predicted to be located in actin filament. [provided by Alliance of Genome Resources, Apr 2022]

RCSD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3963769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCSD1	NM_052862.4 linkuse as main transcript	c.113C>T	p.Pro38Leu	missense_variant	3/7	ENST00000367854.8	NP_443094.3	Q6JBY9-1
RCSD1	NM_001322923.2 linkuse as main transcript	c.108+1424C>T		intron_variant			NP_001309852.1	B7ZKW8
RCSD1	NM_001322924.2 linkuse as main transcript	c.108+1424C>T		intron_variant			NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RCSD1	ENST00000367854.8 linkuse as main transcript	c.113C>T	p.Pro38Leu	missense_variant	3/7	1	NM_052862.4	ENSP00000356828.3	Q6JBY9-1
RCSD1	ENST00000537350.5 linkuse as main transcript	c.108+1424C>T		intron_variant		1		ENSP00000439409.1	B7ZKW8
RCSD1	ENST00000361496.3 linkuse as main transcript	c.113C>T	p.Pro38Leu	missense_variant	3/5	3		ENSP00000355291.3	F6T4W9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250840

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135578

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727010

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

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

Dec 01, 2022

The c.113C>T (p.P38L) alteration is located in exon 3 (coding exon 3) of the RCSD1 gene. This alteration results from a C to T substitution at nucleotide position 113, causing the proline (P) at amino acid position 38 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

1.0

D;.

Vest4

0.53

MutPred

0.26

Loss of glycosylation at P38 (P = 0.0122);Loss of glycosylation at P38 (P = 0.0122);

MVP

0.57

MPC

0.24

ClinPred

0.97

GERP RS

4.1

Varity_R

0.27

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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