dbSNP rs3746887: B3GALT5:p.Met85Lys (chr21-39660813-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001356336.2(B3GALT5):c.254T>A(p.Met85Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,256 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

B3GALT5
NM_001356336.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

0 publications found

Variant links:

Genes affected

B3GALT5 (HGNC:920): (beta-1,3-galactosyltransferase 5) This gene encodes a member of a family of membrane-bound glycoproteins. The encoded protein may synthesize type 1 Lewis antigens, which are elevated in gastrointestinal and pancreatic cancers. Alternatively spliced transcript variants using multiple alternate promoters have been observed for this gene. [provided by RefSeq, Sep 2017]

B3GALT5 links:

ENSG00000225330 (HGNC:):

ENSG00000225330 links:

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ACMG classification

Classification was made for transcript

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=0.030265778).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001356336.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GALT5	NM_001356336.2	MANE Select	c.254T>A	p.Met85Lys	missense	Exon 4 of 4	NP_001343265.1	Q9Y2C3
B3GALT5	NM_033172.3		c.266T>A	p.Met89Lys	missense	Exon 3 of 3	NP_149362.2	A0A0A0MS93
B3GALT5	NM_001278650.2		c.254T>A	p.Met85Lys	missense	Exon 3 of 3	NP_001265579.1	Q9Y2C3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GALT5	ENST00000684187.2	MANE Select	c.254T>A	p.Met85Lys	missense	Exon 4 of 4	ENSP00000506797.1	Q9Y2C3
B3GALT5	ENST00000380618.5	TSL:1	c.254T>A	p.Met85Lys	missense	Exon 3 of 3	ENSP00000369992.1	Q9Y2C3
B3GALT5	ENST00000380620.8	TSL:1	c.254T>A	p.Met85Lys	missense	Exon 5 of 5	ENSP00000369994.3	Q9Y2C3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32930

American (AMR)

AF:

0.00

AC:

AN:

42180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25050

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.00

AC:

AN:

82700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1101874

Other (OTH)

AF:

0.00

AC:

AN:

59558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0020

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.12

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.25

M_CAP

Benign

0.0089

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

PhyloP100

-2.8

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.6

REVEL

Benign

0.033

Sift

Benign

0.87

Sift4G

Benign

0.70

Polyphen

0.024

Vest4

0.065

MutPred

0.42

Gain of methylation at M85 (P = 0.01)

MVP

0.030

MPC

0.36

ClinPred

0.046

GERP RS

-5.7

Varity_R

0.17

gMVP

0.70

Mutation Taster

=94/6

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