1-167697192-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052862.4(RCSD1):c.568G>T(p.Val190Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RCSD1 NM_052862.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.25

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04944679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCSD1	NM_052862.4	c.568G>T	p.Val190Leu	missense_variant	6/7	ENST00000367854.8
RCSD1	NM_001322923.2	c.478G>T	p.Val160Leu	missense_variant	5/6
RCSD1	NM_001322924.2	c.406G>T	p.Val136Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCSD1	ENST00000367854.8	c.568G>T	p.Val190Leu	missense_variant	6/7	1	NM_052862.4	P2
RCSD1	ENST00000537350.5	c.478G>T	p.Val160Leu	missense_variant	5/6	1		A2
RCSD1	ENST00000361496.3	c.496G>T	p.Val166Leu	missense_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Aug 16, 2021

The c.568G>T (p.V190L) alteration is located in exon 6 (coding exon 6) of the RCSD1 gene. This alteration results from a G to T substitution at nucleotide position 568, causing the valine (V) at amino acid position 190 to be replaced by a leucine (L). 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	0.093
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.019
Dann	Benign	0.85
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.13	T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.85	N;N;N
REVEL	Benign	0.010
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0060	B;B;.
Vest4		0.15
MutPred		0.18		.;Loss of sheet (P = 0.0817);.;
MVP		0.33
MPC		0.030
ClinPred		0.084	T
GERP RS		-7.0
Varity_R		0.033
gMVP		0.088

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-167666429;