Genetic Variant NM_178537.5:c.239G>T (chr11-372196-G-T) – 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_178537.5(B4GALNT4):c.239G>T(p.Arg80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,834 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

B4GALNT4
NM_178537.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.63

Publications

0 publications found

Variant links:

Genes affected

B4GALNT4 (HGNC:26315): (beta-1,4-N-acetyl-galactosaminyltransferase 4) Enables acetylgalactosaminyltransferase activity. Predicted to be located in Golgi cisterna membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

B4GALNT4 links:

Genome browser will be placed here

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=0.034226894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT4	NM_178537.5 link	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 20	ENST00000329962.11	NP_848632.2	Q76KP1
B4GALNT4	XM_017017654.2 link	c.-38G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 20		XP_016873143.1
B4GALNT4	XR_001747858.2 link	n.544G>T		non_coding_transcript_exon_variant	Exon 2 of 18
B4GALNT4	XM_017017654.2 link	c.-38G>T		5_prime_UTR_variant	Exon 2 of 20		XP_016873143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT4	ENST00000329962.11 link	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 20	1	NM_178537.5	ENSP00000328277.6		Q76KP1
B4GALNT4	ENST00000530717.1 link	n.247G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000641

AC:

AN:

156020

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397834

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689402

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35732

South Asian (SAS)

AF:

0.00

AC:

AN:

79220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078788

Other (OTH)

AF:

0.00

AC:

AN:

57990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.239G>T (p.R80L) alteration is located in exon 2 (coding exon 2) of the B4GALNT4 gene. This alteration results from a G to T substitution at nucleotide position 239, causing the arginine (R) at amino acid position 80 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.5

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0064

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.62

M_CAP

Benign

0.015

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

PhyloP100

-2.6

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.1

REVEL

Benign

0.030

Sift

Benign

0.59

Sift4G

Benign

0.83

Polyphen

0.36

Vest4

0.23

MutPred

0.14

Loss of helix (P = 0.079);

MVP

0.082

MPC

0.41

ClinPred

0.050

GERP RS

-2.5

Varity_R

0.061

gMVP

0.46

Mutation Taster

=95/5

polymorphism

(source)

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

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NM_178537.5:c.239G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over