chr4-173295403-A-T

Variant names:

Variant summary

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

The NM_017423.3(GALNT7):c.762A>T(p.Leu254Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,426,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

GALNT7
NM_017423.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

GALNT7 (HGNC:4129): (polypeptide N-acetylgalactosaminyltransferase 7) This gene encodes GalNAc transferase 7, a member of the GalNAc-transferase family. The enzyme encoded by this gene controls the initiation step of mucin-type O-linked protein glycosylation and transfer of N-acetylgalactosamine to serine and threonine amino acid residues. This enzyme is a type II transmembrane protein and shares common sequence motifs with other family members. Unlike other family members, this enzyme shows exclusive specificity for partially GalNAc-glycosylated acceptor substrates and shows no activity with non-glycosylated peptides. This protein may function as a follow-up enzyme in the initiation step of O-glycosylation. [provided by RefSeq, Jul 2008]

GALNT7 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, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT7	NM_017423.3 link	c.762A>T	p.Leu254Phe	missense_variant	Exon 4 of 12	ENST00000265000.9	NP_059119.2	Q86SF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT7	ENST00000265000.9 link	c.762A>T	p.Leu254Phe	missense_variant	Exon 4 of 12	1	NM_017423.3	ENSP00000265000.4	Q86SF2
GALNT7	ENST00000505308.6 link	c.762A>T	p.Leu254Phe	missense_variant	Exon 4 of 12	2		ENSP00000427095.2	H0YAH3
GALNT7	ENST00000512285.5 link	c.762A>T	p.Leu254Phe	missense_variant	Exon 4 of 6	5		ENSP00000427050.1	E9PBY3
GALNT7	ENST00000502407.1 link	n.211A>T		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000804

AC:

AN:

248700

AF XY:

0.0000148

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000631

AC:

AN:

1426584

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

711724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32710

American (AMR)

AF:

0.00

AC:

AN:

44436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25832

East Asian (EAS)

AF:

0.00

AC:

AN:

39470

South Asian (SAS)

AF:

0.000106

AC:

AN:

84950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080914

Other (OTH)

AF:

0.00

AC:

AN:

59182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.762A>T (p.L254F) alteration is located in exon 4 (coding exon 4) of the GALNT7 gene. This alteration results from a A to T substitution at nucleotide position 762, causing the leucine (L) at amino acid position 254 to be replaced by a phenylalanine (F). 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.082

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.6

H;.

PhyloP100

1.4

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.68

MutPred

0.67

Gain of methylation at K255 (P = 0.0317);Gain of methylation at K255 (P = 0.0317);

MVP

0.72

MPC

1.3

ClinPred

0.97

GERP RS

3.3

Varity_R

0.85

gMVP

0.75

Mutation Taster

=33/67

disease causing

(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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chr4-173295403-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over