Variant 1-167694103-A-G 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.275A>G(p.Asn92Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,174 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

RCSD1
NM_052862.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

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=0.3684025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCSD1	NM_052862.4 link	c.275A>G	p.Asn92Ser	missense_variant	Exon 5 of 7	ENST00000367854.8	NP_443094.3	Q6JBY9-1
RCSD1	NM_001322923.2 link	c.185A>G	p.Asn62Ser	missense_variant	Exon 4 of 6		NP_001309852.1	B7ZKW8
RCSD1	NM_001322924.2 link	c.113A>G	p.Asn38Ser	missense_variant	Exon 3 of 5		NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RCSD1	ENST00000367854.8 link	c.275A>G	p.Asn92Ser	missense_variant	Exon 5 of 7	1	NM_052862.4	ENSP00000356828.3	Q6JBY9-1
RCSD1	ENST00000537350.5 link	c.185A>G	p.Asn62Ser	missense_variant	Exon 4 of 6	1		ENSP00000439409.1	B7ZKW8
RCSD1	ENST00000361496.3 link	c.203A>G	p.Asn68Ser	missense_variant	Exon 4 of 5	3		ENSP00000355291.3	F6T4W9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Aug 14, 2024

The c.275A>G (p.N92S) alteration is located in exon 5 (coding exon 5) of the RCSD1 gene. This alteration results from a A to G substitution at nucleotide position 275, causing the asparagine (N) at amino acid position 92 to be replaced by a serine (S). 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

0.079

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

D;D;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.5

.;M;.

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.22

T;T;D

Polyphen

0.95

P;D;.

Vest4

0.44

MutPred

0.32

.;Gain of phosphorylation at N92 (P = 0.0582);.;

MVP

0.75

MPC

0.16

ClinPred

0.98

GERP RS

4.0

Varity_R

0.41

gMVP

0.42

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

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