rs3778922

chr7-152105247-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022087.4(GALNT11):c.589G>T(p.Asp197Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000964 in 1,612,470 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.00057 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (59 hom.)
• Consequence: GALNT11 NM_022087.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65

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]

LOC731075 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00860554).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00101 (1468/1460154) while in subpopulation EAS AF= 0.0366 (1450/39662). AF 95% confidence interval is 0.035. There are 59 homozygotes in gnomad4_exome. There are 728 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT11	NM_022087.4	c.589G>T	p.Asp197Tyr	missense_variant, splice_region_variant	5/12	ENST00000430044.7
LOC731075	XR_001745432.2	n.3415-3864C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT11	ENST00000430044.7	c.589G>T	p.Asp197Tyr	missense_variant, splice_region_variant	5/12	5	NM_022087.4	P1
GALNT11	ENST00000434507.5	c.589G>T	p.Asp197Tyr	missense_variant, splice_region_variant	7/14	2		P1
GALNT11	ENST00000447778.5	c.*63G>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	4/7	5

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152198 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000216 AC: 54 AN: 249560 Hom.: 1 AF XY: 0.000215 AC XY: 29 AN XY: 135000

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00268

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00101 AC: 1468 AN: 1460154 Hom.: 59 Cov.: 30 AF XY: 0.00100 AC XY: 728 AN XY: 726462

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0366

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000249

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152316 Hom.: 3 Cov.: 33 AF XY: 0.000671 AC XY: 50 AN XY: 74480

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000212 Hom.: 1

Bravo AF: 0.000178

ExAC AF: 0.000346 AC: 42

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.020
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Benign	0.15
Sift	Benign	0.10	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.53	P;P
Vest4		0.37
MVP		0.65
MPC		0.96
ClinPred		0.16	T
GERP RS		4.4
Varity_R		0.67
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3778922; hg19: chr7-151802332;