3-138130965-A-G

Position:

• chr3-138130965-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000236709.4(A4GNT):​c.292T>C​(p.Ser98Pro) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: A4GNT ENST00000236709.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

Genes affected

A4GNT (HGNC:17968): (alpha-1,4-N-acetylglucosaminyltransferase) This gene encodes a protein from the glycosyltransferase 32 family. The enzyme catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans. It forms a unique glycan, GlcNAcalpha1-->4Galbeta-->R and is largely associated with the Golgi apparatus membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036447078).
• BP6: Variant 3-138130965-A-G is Benign according to our data. Variant chr3-138130965-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2289372.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A4GNT	NM_016161.3	c.292T>C	p.Ser98Pro	missense_variant	2/3	ENST00000236709.4	NP_057245.1
A4GNT	XM_017006543.3	c.292T>C	p.Ser98Pro	missense_variant	2/3		XP_016862032.1
A4GNT	XM_017006544.2	c.292T>C	p.Ser98Pro	missense_variant	2/3		XP_016862033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A4GNT	ENST00000236709.4	c.292T>C	p.Ser98Pro	missense_variant	2/3	1	NM_016161.3	ENSP00000236709.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.7
DANN	Benign	0.96
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.0050	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.047
Sift	Benign	0.32	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.020
MutPred		0.20		Gain of catalytic residue at P97 (P = 0.0186);
MVP		0.18
MPC		0.14
ClinPred		0.042	T
GERP RS		-2.1
Varity_R		0.077
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-137849807;