rs905147291

Variant names:

• chr1-201485361-A-C
• rs905147291
• NM_004078.3:c.427T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-201485361-A-C
• chr1-201485361-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004078.3(CSRP1):​c.427T>G​(p.Cys143Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. C143R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSRP1 NM_004078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32

Genes affected

CSRP1 (HGNC:2469): (cysteine and glycine rich protein 1) This gene encodes a member of the cysteine-rich protein (CSRP) family. This gene family includes a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this gene product occurs in proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRP1	NM_004078.3	c.427T>G	p.Cys143Gly	missense_variant	Exon 5 of 6	ENST00000340006.7	NP_004069.1
CSRP1	NM_001193571.2	c.427T>G	p.Cys143Gly	missense_variant	Exon 5 of 6		NP_001180500.1
CSRP1	NM_001193572.2	c.427T>G	p.Cys143Gly	missense_variant	Exon 5 of 6		NP_001180501.1
CSRP1	NM_001193570.2	c.409T>G	p.Cys137Gly	missense_variant	Exon 5 of 6		NP_001180499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRP1	ENST00000340006.7	c.427T>G	p.Cys143Gly	missense_variant	Exon 5 of 6	1	NM_004078.3	ENSP00000345079.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.81	D;D;D;D;D;D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	1.0	.;D;.;.;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Pathogenic	4.9	H;H;H;H;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-12	D;D;D;D;D;D
REVEL	Pathogenic	0.88
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;.
Polyphen		0.99	D;D;D;D;.;.
Vest4		0.95
MutPred		0.89		Loss of stability (P = 0.0182);Loss of stability (P = 0.0182);Loss of stability (P = 0.0182);Loss of stability (P = 0.0182);.;.;
MVP		0.97
MPC		0.92
ClinPred		1.0	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.97
gMVP		0.90

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: rs905147291; hg19: chr1-201454489;