1-167697424-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_052862.4(RCSD1):c.800G>A(p.Ser267Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RCSD1 NM_052862.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0970

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04087466).
• BP6: Variant 1-167697424-G-A is Benign according to our data. Variant chr1-167697424-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3152761.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCSD1	NM_052862.4	c.800G>A	p.Ser267Asn	missense_variant	6/7	ENST00000367854.8
RCSD1	NM_001322923.2	c.710G>A	p.Ser237Asn	missense_variant	5/6
RCSD1	NM_001322924.2	c.638G>A	p.Ser213Asn	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCSD1	ENST00000367854.8	c.800G>A	p.Ser267Asn	missense_variant	6/7	1	NM_052862.4	P2
RCSD1	ENST00000537350.5	c.710G>A	p.Ser237Asn	missense_variant	5/6	1		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460728 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726556

Gnomad4 AFR exome AF: 0.0000299

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.016
Dann	Benign	0.34
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.41	N;N
REVEL	Benign	0.024
Sift	Benign	0.82	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.35		.;Loss of phosphorylation at S267 (P = 6e-04);
MVP		0.16
MPC		0.030
ClinPred		0.027	T
GERP RS		-7.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.015

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs1050658485; hg19: chr1-167666661;