rs1264119810

Variant names:

• chr19-51630108-G-C
• rs1264119810
• NM_003830.4:c.146C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003830.4(SIGLEC5):​c.146C>G​(p.Ser49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIGLEC5 NM_003830.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.38
• Publications: 0 publications found

Genes affected

SIGLEC5 (HGNC:10874): (sialic acid binding Ig like lectin 5) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. The encoded protein is a member of the CD33-related subset of Siglecs and inhibits the activation of several cell types including monocytes, macrophages and neutrophils. Binding of group B Streptococcus (GBS) to the encoded protein plays a role in GBS immune evasion. [provided by RefSeq, Feb 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0966571).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003830.4. 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
	SIGLEC5	NM_003830.4	MANE Select	c.146C>G	p.Ser49Cys	missense	Exon 2 of 9	NP_003821.1	O15389
	SIGLEC5	NM_001384708.1		c.146C>G	p.Ser49Cys	missense	Exon 2 of 8	NP_001371637.1
	SIGLEC5	NM_001384709.1		c.146C>G	p.Ser49Cys	missense	Exon 2 of 8	NP_001371638.1	A0ABB0MVN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC5	ENST00000683636.1	MANE Select	c.146C>G	p.Ser49Cys	missense	Exon 2 of 9	ENSP00000507738.1	O15389
	SIGLEC5	ENST00000958686.1		c.146C>G	p.Ser49Cys	missense	Exon 2 of 9	ENSP00000628745.1
	SIGLEC5	ENST00000850616.1		c.146C>G	p.Ser49Cys	missense	Exon 2 of 8	ENSP00000520903.1	A0ABB0MVN2

Frequencies

GnomAD3 genomes AF: 0.0000871 AC: 3 AN: 34456 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00187

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000983 AC: 7 AN: 71200 AF XY: 0.000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000651

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000443

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000189 AC: 10 AN: 528842 Hom.: 0 Cov.: 6 AF XY: 0.0000254 AC XY: 7 AN XY: 275774

African (AFR) AF: 0.00 AC: 0 AN: 15062

American (AMR) AF: 0.00 AC: 0 AN: 22584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14678

East Asian (EAS) AF: 0.000283 AC: 9 AN: 31808

South Asian (SAS) AF: 0.00 AC: 0 AN: 51116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2172

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 330686

Other (OTH) AF: 0.0000348 AC: 1 AN: 28716

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000871 AC: 3 AN: 34456 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 15150

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9608

American (AMR) AF: 0.00 AC: 0 AN: 2974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 910

East Asian (EAS) AF: 0.00187 AC: 3 AN: 1606

South Asian (SAS) AF: 0.00 AC: 0 AN: 1286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 190

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 15272

Other (OTH) AF: 0.00 AC: 0 AN: 504

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000343967), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.46
DANN	Benign	0.88
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.023	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-3.4
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.29
Sift	Benign	0.15	T
Sift4G	Uncertain	0.023	D
Polyphen		0.99	D
Vest4		0.19
MutPred		0.72		Gain of catalytic residue at W50 (P = 0.013)
MVP		0.33
ClinPred		0.25	T
GERP RS		-8.5
PromoterAI		-0.061	Neutral
Varity_R		0.22
gMVP		0.090
Mutation Taster		=90/10	polymorphism

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: rs1264119810; hg19: chr19-52133361;