19-51646425-C-G

Position:

• chr19-51646425-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098612.3(SIGLEC14):​c.253G>C​(p.Glu85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 5)
• Consequence: SIGLEC14 NM_001098612.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.402

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14403668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC14	NM_001098612.3	c.253G>C	p.Glu85Gln	missense_variant	2/7	ENST00000360844.7	NP_001092082.1
SIGLEC14	XM_047437991.1	c.253G>C	p.Glu85Gln	missense_variant	2/5		XP_047293947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC14	ENST00000360844.7	c.253G>C	p.Glu85Gln	missense_variant	2/7	1	NM_001098612.3	ENSP00000354090	P1

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 5

Alfa AF: 0.0000936 Hom.: 0

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

Jan 16, 2024

The c.253G>C (p.E85Q) alteration is located in exon 2 (coding exon 2) of the SIGLEC14 gene. This alteration results from a G to C substitution at nucleotide position 253, causing the glutamic acid (E) at amino acid position 85 to be replaced by a glutamine (Q). 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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.24	.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.11
Sift	Benign	0.039	.;D
Sift4G	Benign	0.21	T;T
Polyphen		0.98	.;D
Vest4		0.042
MutPred		0.45		Gain of MoRF binding (P = 0.0265);Gain of MoRF binding (P = 0.0265);
MVP		0.46
MPC		2.5
ClinPred		0.39	T
GERP RS		0.71
Varity_R		0.078
gMVP		0.13

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: rs1984048934; hg19: chr19-52149678;