1-167694237-G-A

Variant names:

• chr1-167694237-G-A
• rs1659444606
• NM_052862.4:c.409G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 in silico tools predict 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: -0.607
• 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: Likely_benign. The variant received -2 ACMG points.

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

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.409G>A	p.Ala137Thr	missense	Exon 5 of 7	NP_443094.3
	RCSD1	NM_001322923.2		c.319G>A	p.Ala107Thr	missense	Exon 4 of 6	NP_001309852.1	B7ZKW8
	RCSD1	NM_001322924.2		c.247G>A	p.Ala83Thr	missense	Exon 3 of 5	NP_001309853.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCSD1	ENST00000367854.8	TSL:1 MANE Select	c.409G>A	p.Ala137Thr	missense	Exon 5 of 7	ENSP00000356828.3	Q6JBY9-1
	RCSD1	ENST00000537350.5	TSL:1	c.319G>A	p.Ala107Thr	missense	Exon 4 of 6	ENSP00000439409.1	B7ZKW8
	RCSD1	ENST00000900257.1		c.319G>A	p.Ala107Thr	missense	Exon 5 of 7	ENSP00000570316.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.61
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.048
Sift	Benign	0.26	T
Sift4G	Benign	0.41	T
Polyphen		0.024	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
Mutation Taster		=93/7	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: rs1659444606; hg19: chr1-167663474;