19-49970510-G-A

Position:

• chr19-49970510-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000602139.6(SIGLEC16):​c.608G>A​(p.Arg203His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 23)
  • Exomes 𝑓: 0.0025 (101 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIGLEC16 ENST00000602139.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.32

Genes affected

SIGLEC16 (HGNC:24851): (sialic acid binding Ig like lectin 16) Predicted to enable sialic acid binding activity. Involved in positive regulation of defense response to bacterium and positive regulation of interleukin-6 production. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-49970510-G-A is Benign according to our data. Variant chr19-49970510-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650296.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC16	NR_145574.2	n.646G>A		non_coding_transcript_exon_variant	3/9
SIGLEC16	NM_001348364.2	c.606G>A	p.Thr202=	synonymous_variant	4/10		NP_001335293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC16	ENST00000602139.6	c.608G>A	p.Arg203His	missense_variant	3/9	5		ENSP00000502223	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 206 AN: 135936 Hom.: 2 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.000715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.00167

GnomAD3 exomes AF: 0.00150 AC: 236 AN: 156940 Hom.: 13 AF XY: 0.00166 AC XY: 139 AN XY: 83830

Gnomad AFR exome AF: 0.000489

Gnomad AMR exome AF: 0.000822

Gnomad ASJ exome AF: 0.000974

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000249

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.00285

Gnomad OTH exome AF: 0.00265

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00254 AC: 3396 AN: 1338302 Hom.: 101 Cov.: 29 AF XY: 0.00244 AC XY: 1619 AN XY: 664306

Gnomad4 AFR exome AF: 0.000316

Gnomad4 AMR exome AF: 0.000830

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.0000578

Gnomad4 SAS exome AF: 0.000259

Gnomad4 FIN exome AF: 0.000156

Gnomad4 NFE exome AF: 0.00311

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00151 AC: 205 AN: 136058 Hom.: 2 Cov.: 23 AF XY: 0.00133 AC XY: 88 AN XY: 65938

Gnomad4 AFR AF: 0.000713

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000203

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.00165

Alfa AF: 0.00255 Hom.: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

SIGLEC16: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.15
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs574891899; hg19: chr19-50473767;