NM_001385465.1:c.306A>G

Variant names:

• chr19-51265778-A-G
• rs141713421
• NM_001385465.1:c.306A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001385465.1(SIGLECL1):​c.306A>G​(p.Arg102Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: SIGLECL1 NM_001385465.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.001161
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.180
• Publications: 1 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-51265778-A-G is Benign according to our data. Variant chr19-51265778-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2650369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.18 with no splicing effect.

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.306A>G	p.Arg102Arg	splice_region synonymous	Exon 4 of 6	NP_001372394.1	Q8N7X8
	SIGLECL1	NM_001385466.1		c.306A>G	p.Arg102Arg	splice_region synonymous	Exon 4 of 6	NP_001372395.1	Q8N7X8
	SIGLECL1	NM_173635.3		c.306A>G	p.Arg102Arg	splice_region synonymous	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.306A>G	p.Arg102Arg	splice_region synonymous	Exon 4 of 6	ENSP00000469601.2	Q8N7X8
	SIGLECL1	ENST00000614422.4	TSL:1	c.306A>G	p.Arg102Arg	splice_region synonymous	Exon 3 of 5	ENSP00000480286.1	Q8N7X8
	SIGLECL1	ENST00000597824.1	TSL:1	c.24A>G	p.Gly8Gly	splice_region synonymous	Exon 2 of 4	ENSP00000472702.1	B7ZLS6

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000517 AC: 130 AN: 251438 AF XY: 0.000449

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.000712

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000454 AC: 664 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 333 AN XY: 727244

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 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: 0.00174 AC: 93 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000479 AC: 533 AN: 1112006

Other (OTH) AF: 0.000248 AC: 15 AN: 60396

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74484

African (AFR) AF: 0.000120 AC: 5 AN: 41570

American (AMR) AF: 0.000196 AC: 3 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000752 Hom.: 1

Bravo AF: 0.000442

EpiCase AF: 0.000763

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.71
PhyloP100		-0.18
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.040
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: rs141713421; hg19: chr19-51769032;