chr19-51645836-T-C

Position:

• chr19-51645836-T-C

Variant summary

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

The NM_001098612.3(SIGLEC14):​c.646A>G​(p.Lys216Glu) 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. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 20)
• Consequence: SIGLEC14 NM_001098612.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.217

Genes affected

SIGLEC14 (HGNC:32926): (sialic acid binding Ig like lectin 14) Predicted to enable sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to be located in ficolin-1-rich granule membrane and tertiary granule membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3	c.646A>G	p.Lys216Glu	missense_variant	3/7	ENST00000360844.7	NP_001092082.1
SIGLEC14	XM_047437991.1	c.646A>G	p.Lys216Glu	missense_variant	3/5		XP_047293947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC14	ENST00000360844.7	c.646A>G	p.Lys216Glu	missense_variant	3/7	1	NM_001098612.3	ENSP00000354090.5

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.646A>G (p.K216E) alteration is located in exon 3 (coding exon 3) of the SIGLEC14 gene. This alteration results from a A to G substitution at nucleotide position 646, causing the lysine (K) at amino acid position 216 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Benign	0.033	D
Sift4G	Benign	0.25	T
Polyphen		0.67	P
Vest4		0.069
MutPred		0.45		Loss of methylation at K216 (P = 0.0109);
MVP		0.46
MPC		0.18
ClinPred		0.073	T
GERP RS		0.76
Varity_R		0.10
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52149089;