chr1-167694237-G-A

Position:

• chr1-167694237-G-A

Variant summary

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

The NM_052862.4(RCSD1):​c.409G>A​(p.Ala137Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCSD1 NM_052862.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.607

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04688558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCSD1	NM_052862.4	c.409G>A	p.Ala137Thr	missense_variant	5/7	ENST00000367854.8	NP_443094.3
RCSD1	NM_001322923.2	c.319G>A	p.Ala107Thr	missense_variant	4/6		NP_001309852.1
RCSD1	NM_001322924.2	c.247G>A	p.Ala83Thr	missense_variant	3/5		NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCSD1	ENST00000367854.8	c.409G>A	p.Ala137Thr	missense_variant	5/7	1	NM_052862.4	ENSP00000356828.3
RCSD1	ENST00000537350.5	c.319G>A	p.Ala107Thr	missense_variant	4/6	1		ENSP00000439409.1
RCSD1	ENST00000361496.3	c.337G>A	p.Ala113Thr	missense_variant	4/5	3		ENSP00000355291.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.409G>A (p.A137T) alteration is located in exon 5 (coding exon 5) of the RCSD1 gene. This alteration results from a G to A substitution at nucleotide position 409, causing the alanine (A) at amino acid position 137 to be replaced by a threonine (T). 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	0.081
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	.;T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	.;N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.048
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.024	B;B;.
Vest4		0.080
MutPred		0.13		.;Gain of phosphorylation at A137 (P = 0.0101);.;
MVP		0.39
MPC		0.031
ClinPred		0.19	T
GERP RS		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.022
gMVP		0.18

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

Other links and lift over

dbSNP: rs1659444606; hg19: chr1-167663474;