1-201488886-T-A

Variant names:

• chr1-201488886-T-A
• rs753999332
• NM_004078.3:c.380A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004078.3(CSRP1):​c.380A>T​(p.Tyr127Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Y127C) 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: 6.25
• Publications: 1 publications found

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]

CSRP1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004078.3. 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
	CSRP1	NM_004078.3	MANE Select	c.380A>T	p.Tyr127Phe	missense	Exon 4 of 6	NP_004069.1	A0A384P5K2
	CSRP1	NM_001193571.2		c.380A>T	p.Tyr127Phe	missense	Exon 4 of 6	NP_001180500.1	P21291
	CSRP1	NM_001193572.2		c.380A>T	p.Tyr127Phe	missense	Exon 4 of 6	NP_001180501.1	A0A384P5K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRP1	ENST00000340006.7	TSL:1 MANE Select	c.380A>T	p.Tyr127Phe	missense	Exon 4 of 6	ENSP00000345079.2	P21291
	CSRP1	ENST00000532313.5	TSL:1	n.378A>T		non_coding_transcript_exon	Exon 3 of 4
	CSRP1	ENST00000533402.5	TSL:1	n.3614A>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.44
Sift	Benign	0.24	T
Sift4G	Benign	0.14	T
Polyphen		0.012	B
Vest4		0.45
MutPred		0.56		Loss of phosphorylation at Y127 (P = 0.0302)
MVP		0.85
MPC		0.26
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.49
gMVP		0.46
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs753999332; hg19: chr1-201458014;