19-51265807-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385465.1(SIGLECL1):​c.335T>G​(p.Val112Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIGLECL1 NM_001385465.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04714179).

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>G	p.Val112Gly	missense	Exon 4 of 6	NP_001372394.1	Q8N7X8
	SIGLECL1	NM_001385466.1		c.335T>G	p.Val112Gly	missense	Exon 4 of 6	NP_001372395.1	Q8N7X8
	SIGLECL1	NM_173635.3		c.335T>G	p.Val112Gly	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>G	p.Val112Gly	missense	Exon 4 of 6	ENSP00000469601.2	Q8N7X8
	SIGLECL1	ENST00000614422.4	TSL:1	c.335T>G	p.Val112Gly	missense	Exon 3 of 5	ENSP00000480286.1	Q8N7X8
	SIGLECL1	ENST00000597824.1	TSL:1	c.53T>G	p.Val18Gly	missense	Exon 2 of 4	ENSP00000472702.1	B7ZLS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251474 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.16	N
PhyloP100		-0.063
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.050
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.89	P
Vest4		0.22
MutPred		0.40		Loss of stability (P = 0.0152)
MVP		0.11
MPC		0.35
ClinPred		0.092	T
GERP RS		2.1
Varity_R		0.30
gMVP		0.13
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;