chr4-172545782-A-C

Variant names:

• chr4-172545782-A-C
• rs337999
• NM_001034845.3:c.553+197093A>C

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+197093A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,182 control chromosomes in the GnomAD database, including 2,079 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 0.16 (2079 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALNTL6 NM_001034845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNTL6	NM_001034845.3	c.553+197093A>C		intron_variant	Intron 5 of 12	ENST00000506823.6	NP_001030017.2
GALNTL6	XM_017008244.3	c.577+197093A>C		intron_variant	Intron 4 of 11		XP_016863733.1
GALNTL6	XM_011531993.3	c.316+197093A>C		intron_variant	Intron 4 of 11		XP_011530295.1
GALNTL6	XM_017008243.3	c.553+197093A>C		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+197093A>C		intron_variant	Intron 5 of 12	1	NM_001034845.3	ENSP00000423313.1
GALNTL6	ENST00000508122.5	c.502+197093A>C		intron_variant	Intron 4 of 11	1		ENSP00000423827.1
GALNTL6	ENST00000457021.1	n.645+34A>C		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24289 AN: 152064 Hom.: 2062 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.147

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.160 AC: 24342 AN: 152182 Hom.: 2079 Cov.: 32 AF XY: 0.159 AC XY: 11839 AN XY: 74404

African (AFR) AF: 0.223 AC: 9270 AN: 41514

American (AMR) AF: 0.166 AC: 2541 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 295 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5168

South Asian (SAS) AF: 0.117 AC: 564 AN: 4824

European-Finnish (FIN) AF: 0.0997 AC: 1057 AN: 10598

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.130 AC: 8866 AN: 68020

Other (OTH) AF: 0.147 AC: 310 AN: 2116

Alfa AF: 0.142 Hom.: 276

Bravo AF: 0.169

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.9
DANN	Benign	0.67
PhyloP100		0.074
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: rs337999; hg19: chr4-173466933;