19-51645913-G-T

Position:

• chr19-51645913-G-T

Variant summary

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

The NM_001098612.3(SIGLEC14):​c.569C>A​(p.Pro190His) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 17)
• Consequence: SIGLEC14 NM_001098612.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18791687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3	c.569C>A	p.Pro190His	missense_variant	3/7	ENST00000360844.7	NP_001092082.1
SIGLEC14	XM_047437991.1	c.569C>A	p.Pro190His	missense_variant	3/5		XP_047293947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC14	ENST00000360844.7	c.569C>A	p.Pro190His	missense_variant	3/7	1	NM_001098612.3	ENSP00000354090	P1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 17

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

Feb 22, 2023

The c.569C>A (p.P190H) alteration is located in exon 3 (coding exon 3) of the SIGLEC14 gene. This alteration results from a C to A substitution at nucleotide position 569, causing the proline (P) at amino acid position 190 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.058
Sift	Benign	0.047	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.29		Loss of glycosylation at P190 (P = 0.0598);
MVP		0.21
MPC		3.4
ClinPred		0.74	D
GERP RS		2.0
Varity_R		0.32
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52149166;