chr9-131523147-T-C

Variant names:

• chr9-131523147-T-C
• rs3739495
• NM_001077365.2:c.*41T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077365.2(POMT1):​c.*41T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,599,024 control chromosomes in the GnomAD database, including 707,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60506 hom., cov: 32)
  • Exomes 𝑓: 0.94 (646922 hom.)
• Consequence: POMT1 NM_001077365.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.67
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-131523147-T-C is Benign according to our data. Variant chr9-131523147-T-C is described in ClinVar as Benign. ClinVar VariationId is 260136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.947 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.*41T>C		3_prime_UTR	Exon 20 of 20	NP_001070833.1	A0A140VKE0
	POMT1	NM_001353193.2		c.*41T>C		3_prime_UTR	Exon 20 of 20	NP_001340122.2	Q9Y6A1-1
	POMT1	NM_007171.4		c.*41T>C		3_prime_UTR	Exon 20 of 20	NP_009102.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	ENST00000402686.8	TSL:1 MANE Select	c.*41T>C		3_prime_UTR	Exon 20 of 20	ENSP00000385797.4	Q9Y6A1-2
	POMT1	ENST00000372228.9	TSL:1	c.*41T>C		3_prime_UTR	Exon 20 of 20	ENSP00000361302.3	Q9Y6A1-1
	POMT1	ENST00000955372.1		c.*41T>C		3_prime_UTR	Exon 20 of 20	ENSP00000625431.1

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134822 AN: 152056 Hom.: 60474 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.895

GnomAD2 exomes AF: 0.923 AC: 217286 AN: 235412 AF XY: 0.932

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.916

Gnomad FIN exome AF: 0.978

Gnomad NFE exome AF: 0.953

Gnomad OTH exome AF: 0.932

GnomAD4 exome AF: 0.945 AC: 1366829 AN: 1446850 Hom.: 646922 Cov.: 42 AF XY: 0.947 AC XY: 680854 AN XY: 719312

African (AFR) AF: 0.731 AC: 24360 AN: 33340

American (AMR) AF: 0.841 AC: 36926 AN: 43886

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 24356 AN: 25838

East Asian (EAS) AF: 0.918 AC: 36397 AN: 39648

South Asian (SAS) AF: 0.970 AC: 82398 AN: 84908

European-Finnish (FIN) AF: 0.976 AC: 46065 AN: 47182

Middle Eastern (MID) AF: 0.933 AC: 4088 AN: 4380

European-Non Finnish (NFE) AF: 0.954 AC: 1056625 AN: 1107712

Other (OTH) AF: 0.928 AC: 55614 AN: 59956

GnomAD4 genome AF: 0.886 AC: 134896 AN: 152174 Hom.: 60506 Cov.: 32 AF XY: 0.888 AC XY: 66101 AN XY: 74398

African (AFR) AF: 0.743 AC: 30821 AN: 41464

American (AMR) AF: 0.861 AC: 13164 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3266 AN: 3468

East Asian (EAS) AF: 0.920 AC: 4757 AN: 5172

South Asian (SAS) AF: 0.971 AC: 4684 AN: 4826

European-Finnish (FIN) AF: 0.977 AC: 10367 AN: 10606

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64851 AN: 68020

Other (OTH) AF: 0.897 AC: 1897 AN: 2116

Alfa AF: 0.925 Hom.: 86535

Bravo AF: 0.868

Asia WGS AF: 0.918 AC: 3191 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2K (2)
-	-	2	not provided (2)
-	-	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	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3739495; hg19: chr9-134398534;