chr1-201496222-T-A

Variant names:

• chr1-201496222-T-A
• rs34504522
• NM_004078.3:c.82A>T

Variant summary

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

The NM_004078.3(CSRP1):​c.82A>T​(p.Asn28Tyr) 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. 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. N28D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSRP1 NM_004078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 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=0.31617147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRP1	NM_004078.3	c.82A>T	p.Asn28Tyr	missense_variant	Exon 2 of 6	ENST00000340006.7	NP_004069.1
CSRP1	NM_001193571.2	c.82A>T	p.Asn28Tyr	missense_variant	Exon 2 of 6		NP_001180500.1
CSRP1	NM_001193572.2	c.82A>T	p.Asn28Tyr	missense_variant	Exon 2 of 6		NP_001180501.1
CSRP1	NM_001193570.2	c.82A>T	p.Asn28Tyr	missense_variant	Exon 2 of 6		NP_001180499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRP1	ENST00000340006.7	c.82A>T	p.Asn28Tyr	missense_variant	Exon 2 of 6	1	NM_004078.3	ENSP00000345079.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T;T;T;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.91	.;D;D;.;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.21	N;N;.;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.52	N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.28	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;.;B;B
Vest4		0.43
MutPred		0.49		Gain of catalytic residue at N28 (P = 0.0558);Gain of catalytic residue at N28 (P = 0.0558);Gain of catalytic residue at N28 (P = 0.0558);Gain of catalytic residue at N28 (P = 0.0558);Gain of catalytic residue at N28 (P = 0.0558);
MVP		0.85
MPC		0.26
ClinPred		0.38	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.052
gMVP		0.55

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: rs34504522; hg19: chr1-201465350;