rs3746887

chr21-39660813-T-Gchr21-39660813-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001356336.2(B3GALT5):c.254T>G(p.Met85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. M85T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B3GALT5 NM_001356336.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03122583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALT5	NM_001356336.2	c.254T>G	p.Met85Arg	missense_variant	4/4	ENST00000684187.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALT5	ENST00000684187.2	c.254T>G	p.Met85Arg	missense_variant	4/4		NM_001356336.2	P1
	ENST00000416555.1	n.220+30323T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1442258 Hom.: 0 Cov.: 76 AF XY: 0.00 AC XY: 0 AN XY: 715372

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.0020
Dann	Benign	0.53
DEOGEN2	Benign	0.12	T;T;T;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.031	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.57	N;N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.8	N;.;N;N;.
REVEL	Benign	0.024
Sift	Benign	0.51	T;.;T;T;.
Sift4G	Benign	0.55	T;T;T;T;T
Polyphen		0.0040	B;B;B;B;.
Vest4		0.066
MutPred		0.37		Gain of solvent accessibility (P = 0.039);Gain of solvent accessibility (P = 0.039);Gain of solvent accessibility (P = 0.039);Gain of solvent accessibility (P = 0.039);.;
MVP		0.030
MPC		0.35
ClinPred		0.040	T
GERP RS		-5.7
Varity_R		0.20
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3746887; hg19: chr21-41032740;