9-131506100-GT-GTT

Variant names:

• chr9-131506100-G-GT
• rs148086540
• NM_001077365.2:c.123-5dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001077365.2(POMT1):​c.123-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,575,208 control chromosomes in the GnomAD database, including 11,010 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1260 hom., cov: 30)
  • Exomes 𝑓: 0.13 (9750 hom.)
• Consequence: POMT1 NM_001077365.2 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.217
• Publications: 1 publications found

Genes affected

POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

POMT1 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp, G2P
• myopathy caused by variation in POMT1

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive limb-girdle muscular dystrophy type 2K

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with cerebellar involvement

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-131506100-G-GT is Benign according to our data. Variant chr9-131506100-G-GT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077365.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	NM_001077365.2	MANE Select	c.123-5dupT		splice_region intron	N/A	NP_001070833.1	A0A140VKE0
	POMT1	NM_001353193.2		c.123-5dupT		splice_region intron	N/A	NP_001340122.2	Q9Y6A1-1
	POMT1	NM_007171.4		c.123-5dupT		splice_region intron	N/A	NP_009102.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	ENST00000402686.8	TSL:1 MANE Select	c.123-5dupT		splice_region intron	N/A	ENSP00000385797.4	Q9Y6A1-2
	POMT1	ENST00000372228.9	TSL:1	c.123-5dupT		splice_region intron	N/A	ENSP00000361302.3	Q9Y6A1-1
	POMT1	ENST00000423007.6	TSL:1	c.123-5dupT		splice_region intron	N/A	ENSP00000404119.2	A0A1V1FTP4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17701 AN: 151216 Hom.: 1260 Cov.: 30

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00849

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0385

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.115 AC: 27334 AN: 238246 AF XY: 0.114

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.00773

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.132 AC: 188049 AN: 1423874 Hom.: 9750 Cov.: 32 AF XY: 0.130 AC XY: 92066 AN XY: 709008

African (AFR) AF: 0.0566 AC: 1844 AN: 32608

American (AMR) AF: 0.0675 AC: 2966 AN: 43942

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3306 AN: 25462

East Asian (EAS) AF: 0.00643 AC: 244 AN: 37950

South Asian (SAS) AF: 0.0565 AC: 4797 AN: 84922

European-Finnish (FIN) AF: 0.216 AC: 11160 AN: 51696

Middle Eastern (MID) AF: 0.0447 AC: 252 AN: 5632

European-Non Finnish (NFE) AF: 0.145 AC: 156512 AN: 1082976

Other (OTH) AF: 0.119 AC: 6968 AN: 58686

GnomAD4 genome AF: 0.117 AC: 17709 AN: 151334 Hom.: 1260 Cov.: 30 AF XY: 0.120 AC XY: 8865 AN XY: 73900

African (AFR) AF: 0.0623 AC: 2568 AN: 41228

American (AMR) AF: 0.101 AC: 1539 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 434 AN: 3456

East Asian (EAS) AF: 0.00851 AC: 44 AN: 5170

South Asian (SAS) AF: 0.0516 AC: 247 AN: 4784

European-Finnish (FIN) AF: 0.216 AC: 2249 AN: 10404

Middle Eastern (MID) AF: 0.0345 AC: 10 AN: 290

European-Non Finnish (NFE) AF: 0.151 AC: 10257 AN: 67792

Other (OTH) AF: 0.112 AC: 234 AN: 2094

Alfa AF: 0.0823 Hom.: 139

Bravo AF: 0.103

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2K (1)
-	-	1	Congenital muscular dystrophy (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (1)
-	-	1	Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.22
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: rs148086540; hg19: chr9-134381487; COSMIC: COSV100586371; COSMIC: COSV100586371;