19-49970473-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000602139.6(SIGLEC16):c.571G>A(p.Asp191Asn) 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 0.0014 (1 hom., cov: 24)
  • Exomes 𝑓: 0.0014 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIGLEC16 ENST00000602139.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 19-49970473-G-A is Benign according to our data. Variant chr19-49970473-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650295.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC16	NR_145574.2	n.609G>A		non_coding_transcript_exon_variant	3/9
SIGLEC16	NM_001348364.2	c.569G>A	p.Arg190Lys	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC16	ENST00000602139.6	c.571G>A	p.Asp191Asn	missense_variant	3/9	5		P1

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 196 AN: 138068 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00254

Gnomad ASJ AF: 0.000967

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00674

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0503

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.00597

GnomAD3 exomes AF: 0.00206 AC: 409 AN: 198628 Hom.: 6 AF XY: 0.00236 AC XY: 254 AN XY: 107804

Gnomad AFR exome AF: 0.000461

Gnomad AMR exome AF: 0.00340

Gnomad ASJ exome AF: 0.00144

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00472

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00161

Gnomad OTH exome AF: 0.00710

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00138 AC: 1918 AN: 1394802 Hom.: 13 Cov.: 31 AF XY: 0.00154 AC XY: 1068 AN XY: 693324

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.00114

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00426

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000976

Gnomad4 OTH exome AF: 0.00258

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00140 AC: 194 AN: 138184 Hom.: 1 Cov.: 24 AF XY: 0.00160 AC XY: 107 AN XY: 67034

Gnomad4 AFR AF: 0.000338

Gnomad4 AMR AF: 0.00254

Gnomad4 ASJ AF: 0.000967

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00699

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00149

Gnomad4 OTH AF: 0.00537

Alfa AF: 0.00251 Hom.: 2

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, 2023

SIGLEC16: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.71
Dann	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs544619308; hg19: chr19-50473730;