NM_178537.5:c.196G>T

Variant names:

• chr11-372153-G-T
• rs916966978
• NM_178537.5:c.196G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178537.5(B4GALNT4):​c.196G>T​(p.Ala66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,626 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A66T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: B4GALNT4 NM_178537.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 0 publications found

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]

ACMG classification

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=0.104002565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT4	NM_178537.5	c.196G>T	p.Ala66Ser	missense_variant	Exon 2 of 20	ENST00000329962.11	NP_848632.2
B4GALNT4	XR_001747858.2	n.501G>T		non_coding_transcript_exon_variant	Exon 2 of 18
B4GALNT4	XM_017017654.2	c.-81G>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	c.196G>T	p.Ala66Ser	missense_variant	Exon 2 of 20	1	NM_178537.5	ENSP00000328277.6
B4GALNT4	ENST00000530717.1	n.204G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397626 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689302

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078798

Other (OTH) AF: 0.00 AC: 0 AN: 57946

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.4
DANN	Benign	0.97
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.11
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.086
Sift	Benign	0.31	T
Sift4G	Benign	0.29	T
Polyphen		0.68	P
Vest4		0.12
MutPred		0.13		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.15
MPC		0.34
ClinPred		0.36	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.22
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs916966978; hg19: chr11-372153;