Variant chr1-167690085-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052862.4(RCSD1):c.235A>G(p.Lys79Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RCSD1
NM_052862.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RCSD1	NM_052862.4 linkuse as main transcript	c.235A>G	p.Lys79Glu	missense_variant	4/7	ENST00000367854.8	NP_443094.3
RCSD1	NM_001322923.2 linkuse as main transcript	c.145A>G	p.Lys49Glu	missense_variant	3/6		NP_001309852.1
RCSD1	NM_001322924.2 linkuse as main transcript	c.109-4014A>G		intron_variant			NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCSD1	ENST00000367854.8 linkuse as main transcript	c.235A>G	p.Lys79Glu	missense_variant	4/7	1	NM_052862.4	ENSP00000356828	P2	Q6JBY9-1
RCSD1	ENST00000537350.5 linkuse as main transcript	c.145A>G	p.Lys49Glu	missense_variant	3/6	1		ENSP00000439409	A2
RCSD1	ENST00000361496.3 linkuse as main transcript	c.199-4014A>G		intron_variant		3		ENSP00000355291

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251442

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135906

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727232

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:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

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

Apr 20, 2024

The c.235A>G (p.K79E) alteration is located in exon 4 (coding exon 4) of the RCSD1 gene. This alteration results from a A to G substitution at nucleotide position 235, causing the lysine (K) at amino acid position 79 to be replaced by a glutamic acid (E). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

.;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.1

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.19

T;T

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.43

.;Loss of methylation at K79 (P = 6e-04);

MVP

0.83

MPC

0.26

ClinPred

0.97

GERP RS

5.8

Varity_R

0.82

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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