1-201490197-G-C

Variant names:

• chr1-201490197-G-C
• NM_004078.3:c.260C>G

Variant summary

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

The NM_004078.3(CSRP1):​c.260C>G​(p.Ser87Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. S87L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CSRP1 NM_004078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

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=0.32936758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRP1	NM_004078.3	c.260C>G	p.Ser87Trp	missense_variant	Exon 3 of 6	ENST00000340006.7	NP_004069.1
CSRP1	NM_001193571.2	c.260C>G	p.Ser87Trp	missense_variant	Exon 3 of 6		NP_001180500.1
CSRP1	NM_001193572.2	c.260C>G	p.Ser87Trp	missense_variant	Exon 3 of 6		NP_001180501.1
CSRP1	NM_001193570.2	c.260C>G	p.Ser87Trp	missense_variant	Exon 3 of 6		NP_001180499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRP1	ENST00000340006.7	c.260C>G	p.Ser87Trp	missense_variant	Exon 3 of 6	1	NM_004078.3	ENSP00000345079.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461576 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

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	Benign	0.29
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;T;T;T;T;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.61	D
LIST_S2	Pathogenic	0.98	.;D;D;.;.;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.33	T;T;T;T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.5	L;L;.;L;L;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D;D;D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D;.
Polyphen		0.75	P;P;.;P;P;.;.
Vest4		0.56
MutPred		0.36		Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);.;.;
MVP		0.87
MPC		0.50
ClinPred		0.82	D
GERP RS		4.5
Varity_R		0.065
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-201459325;