19-12838667-A-T

Position:

• chr19-12838667-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014975.3(MAST1):​c.83+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,670 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAST1 NM_014975.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249

Genes affected

MAST1 (HGNC:19034): (microtubule associated serine/threonine kinase 1) This gene is a member of the microtubule-associated serine/threonine kinase (MAST) family. The protein encoded by this gene has an N-terminal serine/threonine kinase domain followed by a postsynaptic density protein-95/discs large/zona occludens-1 (PDZ) domain. In mouse and rat, the orthologous protein associates with the cytoskeleton and can bind both beta-2-syntrophin and neuronal nitric oxide synthase (nNOS) through its PDZ domain. In mouse and rat, this protein also co-localizes with dystrophin- and utrophin-associated protein complexes (DAPC/UAPC) in the vascular endothelium of the central nervous system. [provided by RefSeq, May 2017]

HOOK2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 19-12838667-A-T is Benign according to our data. Variant chr19-12838667-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2002262.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST1	NM_014975.3	c.83+12A>T		intron_variant		ENST00000251472.9	NP_055790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST1	ENST00000251472.9	c.83+12A>T		intron_variant		1	NM_014975.3	ENSP00000251472.3
MAST1	ENST00000591495.6	c.71+367A>T		intron_variant		5		ENSP00000466470.1
HOOK2	ENST00000589765.1	n.33-12167T>A		intron_variant		5
MAST1	ENST00000590883.1	n.183+12A>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454670 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723860

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.83

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: rs1252977537; hg19: chr19-12949481;