NM_003830.4:c.26T>C

Variant names:

• chr19-51630310-A-G
• rs778734174
• NM_003830.4:c.26T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003830.4(SIGLEC5):​c.26T>C​(p.Leu9Pro) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00084 (1 hom., cov: 13)
  • Exomes 𝑓: 0.00081 (2 hom.)
• Consequence: SIGLEC5 NM_003830.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010930002).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.26T>C	p.Leu9Pro	missense	Exon 1 of 9	NP_003821.1	O15389
	SIGLEC5	NM_001384708.1		c.26T>C	p.Leu9Pro	missense	Exon 1 of 8	NP_001371637.1
	SIGLEC5	NM_001384709.1		c.26T>C	p.Leu9Pro	missense	Exon 1 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.26T>C	p.Leu9Pro	missense	Exon 1 of 9	ENSP00000507738.1	O15389
	SIGLEC5	ENST00000958686.1		c.26T>C	p.Leu9Pro	missense	Exon 1 of 9	ENSP00000628745.1
	SIGLEC5	ENST00000850616.1		c.26T>C	p.Leu9Pro	missense	Exon 1 of 8	ENSP00000520903.1	A0ABB0MVN2

Frequencies

GnomAD3 genomes AF: 0.000839 AC: 83 AN: 98964 Hom.: 1 Cov.: 13

Gnomad AFR AF: 0.000127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000591

Gnomad ASJ AF: 0.00368

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00120

Gnomad FIN AF: 0.000174

Gnomad MID AF: 0.0147

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000819 AC: 41 AN: 50036 AF XY: 0.000950

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000839

Gnomad ASJ exome AF: 0.00236

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.000814 AC: 570 AN: 700170 Hom.: 2 Cov.: 9 AF XY: 0.000842 AC XY: 298 AN XY: 353886

African (AFR) AF: 0.000306 AC: 5 AN: 16342

American (AMR) AF: 0.000597 AC: 12 AN: 20092

Ashkenazi Jewish (ASJ) AF: 0.00232 AC: 35 AN: 15112

East Asian (EAS) AF: 0.00 AC: 0 AN: 26492

South Asian (SAS) AF: 0.000477 AC: 24 AN: 50318

European-Finnish (FIN) AF: 0.0000343 AC: 1 AN: 29156

Middle Eastern (MID) AF: 0.0114 AC: 28 AN: 2462

European-Non Finnish (NFE) AF: 0.000831 AC: 421 AN: 506712

Other (OTH) AF: 0.00131 AC: 44 AN: 33484

GnomAD4 genome AF: 0.000838 AC: 83 AN: 99040 Hom.: 1 Cov.: 13 AF XY: 0.000846 AC XY: 39 AN XY: 46092

African (AFR) AF: 0.000127 AC: 3 AN: 23660

American (AMR) AF: 0.000590 AC: 6 AN: 10178

Ashkenazi Jewish (ASJ) AF: 0.00368 AC: 10 AN: 2714

East Asian (EAS) AF: 0.00 AC: 0 AN: 1760

South Asian (SAS) AF: 0.00121 AC: 3 AN: 2486

European-Finnish (FIN) AF: 0.000174 AC: 1 AN: 5760

Middle Eastern (MID) AF: 0.0160 AC: 4 AN: 250

European-Non Finnish (NFE) AF: 0.00111 AC: 56 AN: 50302

Other (OTH) AF: 0.00 AC: 0 AN: 1328

Alfa AF: 0.000785 Hom.: 1

ExAC AF: 0.0000746 AC: 4

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
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.1
PrimateAI	Uncertain	0.76	T
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.79		Gain of loop (P = 0.024)
MVP		0.79
ClinPred		0.18	T
GERP RS		3.0
PromoterAI		0.00080	Neutral
Varity_R		0.75
gMVP		0.32
Mutation Taster		=62/38	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: rs778734174; hg19: chr19-52133563;