rs2200257

Variant names:

• chr4-172357262-G-A
• rs2200257
• NM_001034845.3:c.553+8573G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034845.3(GALNTL6):​c.553+8573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,034 control chromosomes in the GnomAD database, including 4,736 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4736 hom., cov: 32)
• Consequence: GALNTL6 NM_001034845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 6 publications found

Genes affected

GALNTL6 (HGNC:33844): (polypeptide N-acetylgalactosaminyltransferase like 6) Enables polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNTL6	NM_001034845.3	c.553+8573G>A		intron_variant	Intron 5 of 12	ENST00000506823.6	NP_001030017.2
GALNTL6	XM_017008244.3	c.577+8573G>A		intron_variant	Intron 4 of 11		XP_016863733.1
GALNTL6	XM_011531993.3	c.316+8573G>A		intron_variant	Intron 4 of 11		XP_011530295.1
GALNTL6	XM_017008243.3	c.553+8573G>A		intron_variant	Intron 5 of 9		XP_016863732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNTL6	ENST00000506823.6	c.553+8573G>A		intron_variant	Intron 5 of 12	1	NM_001034845.3	ENSP00000423313.1
GALNTL6	ENST00000508122.5	c.502+8573G>A		intron_variant	Intron 4 of 11	1		ENSP00000423827.1
GALNTL6	ENST00000457021.1	n.502+8573G>A		intron_variant	Intron 3 of 5	1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35411 AN: 151916 Hom.: 4721 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.233 AC: 35471 AN: 152034 Hom.: 4736 Cov.: 32 AF XY: 0.240 AC XY: 17826 AN XY: 74314

African (AFR) AF: 0.340 AC: 14115 AN: 41462

American (AMR) AF: 0.192 AC: 2930 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1839 AN: 5124

South Asian (SAS) AF: 0.151 AC: 728 AN: 4818

European-Finnish (FIN) AF: 0.314 AC: 3326 AN: 10582

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 11024 AN: 68000

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.186 Hom.: 2174

Bravo AF: 0.233

Asia WGS AF: 0.257 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.41
PhyloP100		-0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2200257; hg19: chr4-173278413;