Genetic Variant SIGLEC6:p.Pro411Ala (chr19-51520213-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001245.7(SIGLEC6):c.1231C>G(p.Pro411Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P411T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SIGLEC6
NM_001245.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Publications

3 publications found

Variant links:

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]

SIGLEC6 links:

ENSG00000268777 (HGNC:):

ENSG00000268777 links:

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ACMG classification

Classification was made for transcript

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=0.1755004).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC6	NM_001245.7	MANE Select	c.1231C>G	p.Pro411Ala	missense	Exon 8 of 8	NP_001236.4
SIGLEC6	NM_198845.6		c.1183C>G	p.Pro395Ala	missense	Exon 7 of 7	NP_942142.3	O43699-3
SIGLEC6	NM_001177547.3		c.1075C>G	p.Pro359Ala	missense	Exon 7 of 7	NP_001171018.1	O43699-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC6	ENST00000425629.8	TSL:2 MANE Select	c.1231C>G	p.Pro411Ala	missense	Exon 8 of 8	ENSP00000401502.2	O43699-1
SIGLEC6	ENST00000343300.8	TSL:1	c.1055C>G	p.Pro352Arg	missense	Exon 6 of 6	ENSP00000345907.4	O43699-2
SIGLEC6	ENST00000391797.3	TSL:1	c.1022C>G	p.Pro341Arg	missense	Exon 6 of 6	ENSP00000375674.3	O43699-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

249268

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.0000448

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25986

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.00

AC:

AN:

85440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106000

Other (OTH)

AF:

0.00

AC:

AN:

59998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.3

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.020

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.55

M_CAP

Benign

0.013

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.93

PhyloP100

1.7

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.14

Sift

Benign

0.11

Sift4G

Benign

0.063

Polyphen

0.47

Vest4

0.17

MutPred

0.37

Loss of disorder (P = 0.0832)

MVP

0.63

MPC

0.19

ClinPred

0.062

GERP RS

2.6

Varity_R

0.097

gMVP

0.081

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over