1-167685436-C-A

Variant names:

• chr1-167685436-C-A
• rs1571096022
• NM_052862.4:c.124C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052862.4(RCSD1):​c.124C>A​(p.Pro42Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P42S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCSD1 NM_052862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052862.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCSD1	NM_052862.4	MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 3 of 7	NP_443094.3
	RCSD1	NM_001322923.2		c.108+1435C>A		intron	N/A	NP_001309852.1	B7ZKW8
	RCSD1	NM_001322924.2		c.108+1435C>A		intron	N/A	NP_001309853.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCSD1	ENST00000367854.8	TSL:1 MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 3 of 7	ENSP00000356828.3	Q6JBY9-1
	RCSD1	ENST00000537350.5	TSL:1	c.108+1435C>A		intron	N/A	ENSP00000439409.1	B7ZKW8
	RCSD1	ENST00000900258.1		c.124C>A	p.Pro42Thr	missense	Exon 3 of 6	ENSP00000570317.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.43		Gain of phosphorylation at P42 (P = 0.0056)
MVP		0.87
MPC		0.25
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.37
gMVP		0.32
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs1571096022; hg19: chr1-167654673;