rs3819726

chr6-119186808-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005907.4(MAN1A1):c.1719+1597A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,026 control chromosomes in the GnomAD database, including 4,616 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 0.24 (4616 hom., cov: 31)
• Consequence: MAN1A1 NM_005907.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

Genes affected

MAN1A1 (HGNC:6821): (mannosidase alpha class 1A member 1) This gene encodes a class I mammalian Golgi 1,2-mannosidase which is a type II transmembrane protein. This protein catalyzes the hydrolysis of three terminal mannose residues from peptide-bound Man(9)-GlcNAc(2) oligosaccharides and belongs to family 47 of glycosyl hydrolases. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN1A1	NM_005907.4	c.1719+1597A>T		intron_variant		ENST00000368468.4
MAN1A1	XM_005266986.5	c.1968+1597A>T		intron_variant
MAN1A1	XM_011535833.3	c.1152+1597A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1A1	ENST00000368468.4	c.1719+1597A>T		intron_variant		2	NM_005907.4	P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36115 AN: 151908 Hom.: 4621 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.238 AC: 36134 AN: 152026 Hom.: 4616 Cov.: 31 AF XY: 0.244 AC XY: 18136 AN XY: 74316

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.245

Alfa AF: 0.209 Hom.: 478

Bravo AF: 0.251

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.42
Dann	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs3819726; hg19: chr6-119507973; COSMIC: COSV63786884;