chr19-12840441-C-T

Variant names:

• chr19-12840441-C-T
• NM_014975.3:c.84-5C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014975.3(MAST1):​c.84-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAST1 NM_014975.3 splice_region, intron
• Scores: Splicing: ADA: 0.00005555
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45
• Publications: 0 publications found

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:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-12840441-C-T is Benign according to our data. Variant chr19-12840441-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3671392.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014975.3. 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
	MAST1	NM_014975.3	MANE Select	c.84-5C>T		splice_region intron	N/A	NP_055790.1	Q9Y2H9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST1	ENST00000251472.9	TSL:1 MANE Select	c.84-5C>T		splice_region intron	N/A	ENSP00000251472.3	Q9Y2H9
	MAST1	ENST00000591495.6	TSL:5	c.72-5C>T		splice_region intron	N/A	ENSP00000466470.1	K7EME4
	HOOK2	ENST00000589765.1	TSL:5	n.33-13941G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457322 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725030

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108624

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.7
DANN	Benign	0.93
PhyloP100		-1.4
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.0080
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

hg19: chr19-12951255;