chr1-167685446-G-A

Position:

• chr1-167685446-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052862.4(RCSD1):​c.134G>A​(p.Arg45Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCSD1 NM_052862.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4164406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCSD1	NM_052862.4	c.134G>A	p.Arg45Lys	missense_variant	3/7	ENST00000367854.8	NP_443094.3
RCSD1	NM_001322923.2	c.108+1445G>A		intron_variant			NP_001309852.1
RCSD1	NM_001322924.2	c.108+1445G>A		intron_variant			NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCSD1	ENST00000367854.8	c.134G>A	p.Arg45Lys	missense_variant	3/7	1	NM_052862.4	ENSP00000356828	P2
RCSD1	ENST00000537350.5	c.108+1445G>A		intron_variant		1		ENSP00000439409	A2
RCSD1	ENST00000361496.3	c.134G>A	p.Arg45Lys	missense_variant	3/5	3		ENSP00000355291

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 21, 2022

The c.134G>A (p.R45K) alteration is located in exon 3 (coding exon 3) of the RCSD1 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the arginine (R) at amino acid position 45 to be replaced by a lysine (K). 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	0.28
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;T
Sift4G	Benign	0.16	T;D
Polyphen		1.0	D;.
Vest4		0.40
MutPred		0.30		Gain of methylation at R45 (P = 0.0047);Gain of methylation at R45 (P = 0.0047);
MVP		0.88
MPC		0.24
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.61
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-167654683;