19-51529853-C-A

Variant names:

• chr19-51529853-C-A
• rs370040093
• NM_001245.7:c.883G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001245.7(SIGLEC6):​c.883G>T​(p.Ala295Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC6 NM_001245.7 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.560

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078487664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC6	NM_001245.7	c.883G>T	p.Ala295Ser	missense_variant	Exon 5 of 8	ENST00000425629.8	NP_001236.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC6	ENST00000425629.8	c.883G>T	p.Ala295Ser	missense_variant	Exon 5 of 8	2	NM_001245.7	ENSP00000401502.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

-

Prostate Cancer Research Center, Institute of Biosciences and Medical Technology, University of Tampere

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	1.6
DANN	Benign	0.55
DEOGEN2	Benign	0.0034	.;.;.;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.48	T;T;T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.078	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	.;.;.;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.81	.;N;N;N;N;.
REVEL	Benign	0.13
Sift	Benign	0.37	.;T;T;T;T;.
Sift4G	Benign	0.31	T;T;T;T;T;T
Polyphen		0.15	B;.;.;P;B;B
Vest4		0.11
MutPred		0.41		.;.;.;Loss of catalytic residue at A295 (P = 0.0422);Loss of catalytic residue at A295 (P = 0.0422);.;
MVP		0.16
MPC		0.23
ClinPred		0.13	T
GERP RS		-6.8
Varity_R		0.14
gMVP		0.046

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: rs370040093; hg19: chr19-52033107; COSMIC: COSV58432384; COSMIC: COSV58432384;