1-167694132-C-T

Position:

• chr1-167694132-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052862.4(RCSD1):​c.304C>T​(p.Pro102Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.58

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCSD1	NM_052862.4	c.304C>T	p.Pro102Ser	missense_variant	5/7	ENST00000367854.8	NP_443094.3
RCSD1	NM_001322923.2	c.214C>T	p.Pro72Ser	missense_variant	4/6		NP_001309852.1
RCSD1	NM_001322924.2	c.142C>T	p.Pro48Ser	missense_variant	3/5		NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCSD1	ENST00000367854.8	c.304C>T	p.Pro102Ser	missense_variant	5/7	1	NM_052862.4	ENSP00000356828.3
RCSD1	ENST00000537350.5	c.214C>T	p.Pro72Ser	missense_variant	4/6	1		ENSP00000439409.1
RCSD1	ENST00000361496.3	c.232C>T	p.Pro78Ser	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

Aug 14, 2024

The c.304C>T (p.P102S) alteration is located in exon 5 (coding exon 5) of the RCSD1 gene. This alteration results from a C to T substitution at nucleotide position 304, causing the proline (P) at amino acid position 102 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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Pathogenic	3.0	.;M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.0	D;D;D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.035	D;T;D
Polyphen		1.0	D;D;.
Vest4		0.80
MutPred		0.40		.;Gain of helix (P = 0.0325);.;
MVP		0.92
MPC		0.24
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.79
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-167663369;