7-152094423-G-C

Position:

• chr7-152094423-G-C

Variant summary

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

The NM_001371468.1(GALNT11):​c.-102G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,614,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: GALNT11 NM_001371468.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.186

Genes affected

GALNT11 (HGNC:19875): (polypeptide N-acetylgalactosaminyltransferase 11) Enables Notch binding activity and polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GALNT11 (HGNC:):

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=0.007533461).
• BP6: Variant 7-152094423-G-C is Benign according to our data. Variant chr7-152094423-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2403795.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT11	NM_022087.4	c.196G>C	p.Val66Leu	missense_variant	2/12	ENST00000430044.7	NP_071370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT11	ENST00000430044.7	c.196G>C	p.Val66Leu	missense_variant	2/12	5	NM_022087.4	ENSP00000395122.2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000370 AC: 93 AN: 251312 Hom.: 0 AF XY: 0.000361 AC XY: 49 AN XY: 135834

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000144 AC: 210 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.000147 AC XY: 107 AN XY: 727238

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00348

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000234

Gnomad4 OTH exome AF: 0.000464

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74452

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000319 Hom.: 0

Bravo AF: 0.000253

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000198 AC: 24

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

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

Aug 03, 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	0.076
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.0
DANN	Benign	0.33
DEOGEN2	Benign	0.0024	T;T;.;T;T;.;.;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.59	.;T;T;T;T;.;T;T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.0075	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.81	L;.;.;.;L;L;L;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.060	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.66	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.85	T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;B;B;B;.;.
Vest4		0.17
MutPred		0.33		Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);Gain of catalytic residue at V66 (P = 0.0203);
MVP		0.45
MPC		0.26
ClinPred		0.024	T
GERP RS		0.045
Varity_R		0.052
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs184074640; hg19: chr7-151791508;