19-51528229-C-T

Variant summary

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

The NM_001245.7(SIGLEC6):c.1037G>A(p.Gly346Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,614,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: SIGLEC6 NM_001245.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19

Genes affected

SIGLEC6 (HGNC:10875): (sialic acid binding Ig like lectin 6) This gene encodes a member of the SIGLEC (sialic acid binding immunoglobulin-like lectin) family of proteins. The encoded transmembrane receptor binds sialyl-TN glycans and leptin. Placental expression of the encoded protein is upregulated in preeclampsia. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008871019).
• BP6: Variant 19-51528229-C-T is Benign according to our data. Variant chr19-51528229-C-T is described in ClinVar as [Benign]. Clinvar id is 729001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC6	NM_001245.7	c.1037G>A	p.Gly346Asp	missense_variant	6/8	ENST00000425629.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC6	ENST00000425629.8	c.1037G>A	p.Gly346Asp	missense_variant	6/8	2	NM_001245.7	P2

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 382 AN: 152192 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00847

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000565 AC: 141 AN: 249560 Hom.: 0 AF XY: 0.000384 AC XY: 52 AN XY: 135390

Gnomad AFR exome AF: 0.00756

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000271 AC: 396 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.000209 AC XY: 152 AN XY: 727226

Gnomad4 AFR exome AF: 0.00851

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.000695

GnomAD4 genome AF: 0.00251 AC: 382 AN: 152310 Hom.: 2 Cov.: 31 AF XY: 0.00251 AC XY: 187 AN XY: 74472

Gnomad4 AFR AF: 0.00845

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.0464 Hom.: 2354

Bravo AF: 0.00303

ESP6500AA AF: 0.00786 AC: 31

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000670 AC: 81

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.25
Dann	Benign	0.58
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00089	N
LIST_S2	Benign	0.34	T;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0089	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.36	T
REVEL	Benign	0.11
Sift4G	Benign	0.63	T;T;T;T
Polyphen		0.99	D;.;.;B
Vest4		0.20
MVP		0.27
MPC		0.20
ClinPred		0.034	T
GERP RS		-5.0
Varity_R		0.047
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs182869426; hg19: chr19-52031483;