1-167683939-G-C

Variant names:

• chr1-167683939-G-C
• rs1246446943
• NM_052862.4:c.46G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052862.4(RCSD1):​c.46G>C​(p.Ala16Pro) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A16T) 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: 1.88

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20763832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCSD1	NM_052862.4	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 7	ENST00000367854.8	NP_443094.3
RCSD1	NM_001322923.2	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 6		NP_001309852.1
RCSD1	NM_001322924.2	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 5		NP_001309853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCSD1	ENST00000367854.8	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 7	1	NM_052862.4	ENSP00000356828.3
RCSD1	ENST00000537350.5	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 6	1		ENSP00000439409.1
RCSD1	ENST00000361496.3	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 5	3		ENSP00000355291.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	.;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.040	D;D;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.69	P;D;.
Vest4		0.50
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.80
MPC		0.24
ClinPred		0.63	D
GERP RS		3.3
Varity_R		0.14
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs1246446943; hg19: chr1-167653176;