NM_052862.4:c.62C>T

Variant names:

• chr1-167683955-C-T
• rs752743010
• NM_052862.4:c.62C>T

Variant summary

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

The NM_052862.4(RCSD1):​c.62C>T​(p.Ala21Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A21G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RCSD1 NM_052862.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.41728663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCSD1	NM_052862.4	c.62C>T	p.Ala21Val	missense_variant	Exon 2 of 7	ENST00000367854.8	NP_443094.3
RCSD1	NM_001322923.2	c.62C>T	p.Ala21Val	missense_variant	Exon 2 of 6		NP_001309852.1
RCSD1	NM_001322924.2	c.62C>T	p.Ala21Val	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.62C>T	p.Ala21Val	missense_variant	Exon 2 of 7	1	NM_052862.4	ENSP00000356828.3
RCSD1	ENST00000537350.5	c.62C>T	p.Ala21Val	missense_variant	Exon 2 of 6	1		ENSP00000439409.1
RCSD1	ENST00000361496.3	c.62C>T	p.Ala21Val	missense_variant	Exon 2 of 5	3		ENSP00000355291.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251122 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461828 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	.;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Uncertain	-0.055	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.17
Sift	Benign	0.041	D;D;T
Sift4G	Uncertain	0.017	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.74
MutPred		0.26		Loss of methylation at R26 (P = 0.128);Loss of methylation at R26 (P = 0.128);Loss of methylation at R26 (P = 0.128);
MVP		0.90
MPC		0.24
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.44

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: rs752743010; hg19: chr1-167653192;