5-170246108-A-G

Variant names:

• chr5-170246108-A-G
• rs777378591
• NM_001102609.3:c.241A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102609.3(C5orf58):​c.241A>G​(p.Ile81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 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. I81L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: C5orf58 NM_001102609.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• Publications: 0 publications found

Genes affected

C5orf58 (HGNC:37272): (chromosome 5 open reading frame 58)

LCP2 (HGNC:6529): (lymphocyte cytosolic protein 2) This gene encodes an adapter protein that acts as a substrate of the T cell antigen receptor (TCR)-activated protein tyrosine kinase pathway. The encoded protein associates with growth factor receptor bound protein 2, and is thought to play a role TCR-mediated intracellular signal transduction. A similar protein in mouse plays a role in normal T-cell development and activation. Mice lacking this gene show subcutaneous and intraperitoneal fetal hemorrhaging, dysfunctional platelets and impaired viability. [provided by RefSeq, Nov 2016]

LCP2 Gene-Disease associations (from GenCC):

• immunodeficiency 81

  Inheritance: AR, Unknown Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046171784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102609.3. 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
	C5orf58	NM_001102609.3	MANE Select	c.241A>G	p.Ile81Val	missense	Exon 4 of 4	NP_001096079.2	C9J3I9
	C5orf58	NM_001305393.2		c.241A>G	p.Ile81Val	missense	Exon 4 of 4	NP_001292322.2	C9J3I9
	C5orf58	NM_001305394.2		c.241A>G	p.Ile81Val	missense	Exon 4 of 4	NP_001292323.2	C9J3I9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5orf58	ENST00000593851.5	TSL:2 MANE Select	c.241A>G	p.Ile81Val	missense	Exon 4 of 4	ENSP00000490013.2	C9J3I9
	C5orf58	ENST00000524171.5	TSL:1	c.95-5540A>G		intron	N/A	ENSP00000490552.1	A0A1B0GVU6
	C5orf58	ENST00000521850.5	TSL:1	n.1993A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 244958 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455514 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 723948

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.0000458 AC: 2 AN: 43712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109100

Other (OTH) AF: 0.00 AC: 0 AN: 60132

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.054
DANN	Benign	0.59
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0081	N
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.84
MVP		0.014
ClinPred		0.047	T
GERP RS		-11
gMVP		0.0023
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs777378591; hg19: chr5-169673112;