chr21-39660813-T-G

Variant names:

• chr21-39660813-T-G
• rs3746887
• NM_001356336.2:c.254T>G

Variant summary

Our verdict is Likely benign. The variant received -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. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B3GALT5 NM_001356336.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 43 publications found

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]

ENSG00000225330 (HGNC:):

ACMG classification

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=0.03122583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT5	NM_001356336.2	c.254T>G	p.Met85Arg	missense_variant	Exon 4 of 4	ENST00000684187.2	NP_001343265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALT5	ENST00000684187.2	c.254T>G	p.Met85Arg	missense_variant	Exon 4 of 4		NM_001356336.2	ENSP00000506797.1

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

African (AFR) AF: 0.00 AC: 0 AN: 32930

American (AMR) AF: 0.00 AC: 0 AN: 42180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.00 AC: 0 AN: 82700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101876

Other (OTH) AF: 0.00 AC: 0 AN: 59558

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 220305

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
LIST_S2	Benign	0.14	.;.;.;T;T
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;.
PhyloP100		-2.8
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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs3746887; hg19: chr21-41032740;