Genetic Variant NM_024572.4:c.1600G>T (chr2-30910960-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024572.4(GALNT14):c.1600G>T(p.Val534Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V534I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GALNT14
NM_024572.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

Publications

0 publications found

Variant links:

Genes affected

GALNT14 (HGNC:22946): (polypeptide N-acetylgalactosaminyltransferase 14) This gene encodes a Golgi protein which is a member of the polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-Ts) protein family. These enzymes catalyze the transfer of N-acetyl-D-galactosamine (GalNAc) to the hydroxyl groups on serines and threonines in target peptides. The encoded protein has been shown to transfer GalNAc to large proteins like mucins. Alterations in this gene may play a role in cancer progression and response to chemotherapy. [provided by RefSeq, Jun 2016]

GALNT14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.783

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024572.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GALNT14	NM_024572.4	MANE Select	c.1600G>T	p.Val534Phe	missense	Exon 15 of 15	NP_078848.2	Q96FL9-1
GALNT14	NM_001253826.2		c.1615G>T	p.Val539Phe	missense	Exon 16 of 16	NP_001240755.1	Q96FL9-3
GALNT14	NM_001253827.2		c.1540G>T	p.Val514Phe	missense	Exon 17 of 17	NP_001240756.1	Q96FL9-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GALNT14	ENST00000349752.10	TSL:1 MANE Select	c.1600G>T	p.Val534Phe	missense	Exon 15 of 15	ENSP00000288988.6	Q96FL9-1
GALNT14	ENST00000324589.9	TSL:2	c.1615G>T	p.Val539Phe	missense	Exon 16 of 16	ENSP00000314500.5	Q96FL9-3
GALNT14	ENST00000406653.5	TSL:2	c.1540G>T	p.Val514Phe	missense	Exon 17 of 17	ENSP00000385435.1	Q96FL9-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.4

PhyloP100

3.8

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.38

Sift

Uncertain

0.026

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.81

MutPred

0.55

Loss of methylation at K531 (P = 0.1297)

MVP

0.82

MPC

0.99

ClinPred

0.97

GERP RS

5.3

Varity_R

0.67

gMVP

0.76

Mutation Taster

=59/41

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over