NM_001245.7:c.1352T>C

Variant names:

• chr19-51520092-A-G
• rs1250290911
• NM_001245.7:c.1352T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001245.7(SIGLEC6):​c.1352T>C​(p.Ile451Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIGLEC6 NM_001245.7 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.639
• Publications: 1 publications found

Genes affected

SIGLEC6 (HGNC:10875): (sialic acid binding Ig like lectin 6) This gene encodes a member of the SIGLEC (sialic acid binding immunoglobulin-like lectin) family of proteins. The encoded transmembrane receptor binds sialyl-TN glycans and leptin. Placental expression of the encoded protein is upregulated in preeclampsia. [provided by RefSeq, Jul 2016]

ENSG00000268777 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04682514).
• BP6: Variant 19-51520092-A-G is Benign according to our data. Variant chr19-51520092-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3795968.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001245.7. 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
	SIGLEC6	NM_001245.7	MANE Select	c.1352T>C	p.Ile451Thr	missense	Exon 8 of 8	NP_001236.4
	SIGLEC6	NM_198845.6		c.1304T>C	p.Ile435Thr	missense	Exon 7 of 7	NP_942142.3	O43699-3
	SIGLEC6	NM_001177547.3		c.1196T>C	p.Ile399Thr	missense	Exon 7 of 7	NP_001171018.1	O43699-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC6	ENST00000425629.8	TSL:2 MANE Select	c.1352T>C	p.Ile451Thr	missense	Exon 8 of 8	ENSP00000401502.2	O43699-1
	SIGLEC6	ENST00000343300.8	TSL:1	c.*114T>C		3_prime_UTR	Exon 6 of 6	ENSP00000345907.4	O43699-2
	SIGLEC6	ENST00000391797.3	TSL:1	c.*114T>C		3_prime_UTR	Exon 6 of 6	ENSP00000375674.3	O43699-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1416866 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 699670

African (AFR) AF: 0.00 AC: 0 AN: 32916

American (AMR) AF: 0.00 AC: 0 AN: 44058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 38808

South Asian (SAS) AF: 0.00 AC: 0 AN: 81054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078584

Other (OTH) AF: 0.00 AC: 0 AN: 58174

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.2
DANN	Benign	0.62
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.61	N
PhyloP100		-0.64
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.035
Sift	Benign	0.19	T
Sift4G	Benign	0.40	T
Polyphen		0.24	B
Vest4		0.027
MutPred		0.28		Loss of stability (P = 0.0043)
MVP		0.15
MPC		0.18
ClinPred		0.035	T
GERP RS		-3.0
Varity_R		0.052
gMVP		0.072
Mutation Taster		=98/2	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: rs1250290911; hg19: chr19-52023346;