19-51265448-C-A

Variant names:

• chr19-51265448-C-A
• rs1428342323
• NM_001385465.1:c.103C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001385465.1(SIGLECL1):​c.103C>A​(p.Pro35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SIGLECL1 NM_001385465.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

SIGLECL1 (HGNC:26856): (SIGLEC family like 1) Predicted to enable sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268595 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385465.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLECL1	NM_001385465.1	MANE Select	c.103C>A	p.Pro35Thr	missense	Exon 3 of 6	NP_001372394.1	Q8N7X8
	SIGLECL1	NM_001385466.1		c.103C>A	p.Pro35Thr	missense	Exon 3 of 6	NP_001372395.1	Q8N7X8
	SIGLECL1	NM_173635.3		c.103C>A	p.Pro35Thr	missense	Exon 3 of 6	NP_775906.1	Q8N7X8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLECL1	ENST00000601727.6	TSL:3 MANE Select	c.103C>A	p.Pro35Thr	missense	Exon 3 of 6	ENSP00000469601.2	Q8N7X8
	SIGLECL1	ENST00000614422.4	TSL:1	c.103C>A	p.Pro35Thr	missense	Exon 2 of 5	ENSP00000480286.1	Q8N7X8
	SIGLECL1	ENST00000597824.1	TSL:1	c.23-329C>A		intron	N/A	ENSP00000472702.1	B7ZLS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Benign	0.15
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.055	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.3
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.75		Gain of catalytic residue at P35 (P = 0.0556)
MVP		0.58
MPC		0.91
ClinPred		1.0	D
GERP RS		2.8
Varity_R		0.47
gMVP		0.51
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1428342323; hg19: chr19-51768702; COSMIC: COSV108144981; COSMIC: COSV108144981;