6-119186808-T-A

Variant names:

• chr6-119186808-T-A
• rs3819726
• NM_005907.4:c.1719+1597A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1A1	NM_005907.4	MANE Select	c.1719+1597A>T		intron	N/A	NP_005898.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1A1	ENST00000368468.4	TSL:2 MANE Select	c.1719+1597A>T		intron	N/A	ENSP00000357453.3

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

African (AFR) AF: 0.237 AC: 9835 AN: 41438

American (AMR) AF: 0.374 AC: 5711 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3468

East Asian (EAS) AF: 0.192 AC: 990 AN: 5162

South Asian (SAS) AF: 0.433 AC: 2085 AN: 4818

European-Finnish (FIN) AF: 0.187 AC: 1980 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13921 AN: 67988

Other (OTH) AF: 0.245 AC: 517 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.78
PhyloP100		-0.71
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: rs3819726; hg19: chr6-119507973; COSMIC: COSV63786884;