rs1554772428

chr9-131507372-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001077365.2(POMT1):c.285C>T(p.Tyr95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: POMT1 NM_001077365.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.436

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-131507372-C-T is Benign according to our data. Variant chr9-131507372-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 471380.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT1	NM_001077365.2	c.285C>T	p.Tyr95=	synonymous_variant	5/20	ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8	c.285C>T	p.Tyr95=	synonymous_variant	5/20	1	NM_001077365.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 01, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	3.6
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.29		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554772428; hg19: chr9-134382759;