Variant chr1-167694266-G-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.438G>T(p.Gln146His) 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 152,148 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: 1.72

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=0.29908192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RCSD1	NM_052862.4 linkuse as main transcript	c.438G>T	p.Gln146His	missense_variant	5/7	ENST00000367854.8	NP_443094.3
RCSD1	NM_001322923.2 linkuse as main transcript	c.348G>T	p.Gln116His	missense_variant	4/6		NP_001309852.1
RCSD1	NM_001322924.2 linkuse as main transcript	c.276G>T	p.Gln92His	missense_variant	3/5		NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCSD1	ENST00000367854.8 linkuse as main transcript	c.438G>T	p.Gln146His	missense_variant	5/7	1	NM_052862.4	ENSP00000356828	P2	Q6JBY9-1
RCSD1	ENST00000537350.5 linkuse as main transcript	c.348G>T	p.Gln116His	missense_variant	4/6	1		ENSP00000439409	A2
RCSD1	ENST00000361496.3 linkuse as main transcript	c.366G>T	p.Gln122His	missense_variant	4/5	3		ENSP00000355291

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251236

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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

Mar 02, 2023

The c.438G>T (p.Q146H) alteration is located in exon 5 (coding exon 5) of the RCSD1 gene. This alteration results from a G to T substitution at nucleotide position 438, causing the glutamine (Q) at amino acid position 146 to be replaced by a histidine (H). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

.;M;.

MutationTaster

Benign

0.92

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.57

MutPred

0.23

.;Gain of glycosylation at S151 (P = 0.1013);.;

MVP

0.71

MPC

0.23

ClinPred

0.88

GERP RS

2.9

Varity_R

0.16

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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