19-51265807-T-A

Variant names:

• chr19-51265807-T-A
• rs755691515
• NM_001385465.1:c.335T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385465.1(SIGLECL1):​c.335T>A​(p.Val112Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V112G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLECL1 NM_001385465.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07117951).

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.335T>A	p.Val112Glu	missense	Exon 4 of 6	NP_001372394.1	Q8N7X8
	SIGLECL1	NM_001385466.1		c.335T>A	p.Val112Glu	missense	Exon 4 of 6	NP_001372395.1	Q8N7X8
	SIGLECL1	NM_173635.3		c.335T>A	p.Val112Glu	missense	Exon 4 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.335T>A	p.Val112Glu	missense	Exon 4 of 6	ENSP00000469601.2	Q8N7X8
	SIGLECL1	ENST00000614422.4	TSL:1	c.335T>A	p.Val112Glu	missense	Exon 3 of 5	ENSP00000480286.1	Q8N7X8
	SIGLECL1	ENST00000597824.1	TSL:1	c.53T>A	p.Val18Glu	missense	Exon 2 of 4	ENSP00000472702.1	B7ZLS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.063
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.084
Sift	Benign	0.054	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.89	P
Vest4		0.33
MutPred		0.41		Gain of solvent accessibility (P = 0.0078)
MVP		0.095
MPC		0.43
ClinPred		0.29	T
GERP RS		2.1
Varity_R		0.21
gMVP		0.16
Mutation Taster		=99/1	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: rs755691515; hg19: chr19-51769061;