19-17606022-CAGGCGCAGTGCCGCTCGGCCGACCGCCCGCGCTA-C

Position:

• chr19-17606022-CAGGCGCAGTGCCGCTCGGCCGACCGCCCGCGCTA-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001080421.3(UNC13A):​c.5110_*31del variant causes a stop lost, 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UNC13A NM_001080421.3 stop_lost, 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

Genes affected

UNC13A (HGNC:23150): (unc-13 homolog A) This gene encodes a member of the UNC13 family. UNC13 proteins bind to phorbol esters and diacylglycerol and play important roles in neurotransmitter release at synapses. Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001080421.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13A	NM_001080421.3	c.5110_*31del		stop_lost, 3_prime_UTR_variant	44/44	ENST00000519716.7	NP_001073890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13A	ENST00000519716.7	c.5110_*31del		stop_lost, 3_prime_UTR_variant	44/44	5	NM_001080421.3	ENSP00000429562	A2
UNC13A	ENST00000550896.1			coding_sequence_variant, 3_prime_UTR_variant	40/40	5		ENSP00000446831	A2
UNC13A	ENST00000551649.5	c.5167_*31del		stop_lost, 3_prime_UTR_variant	45/45	5		ENSP00000447236	P3
UNC13A	ENST00000552293.5	c.5092_*31del		stop_lost, 3_prime_UTR_variant	42/42	5		ENSP00000447572	A2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Nov 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17716831;