rs890020457

Variant names:

• chr19-17606132-G-A
• rs890020457
• NM_001080421.3:c.5034C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-17606132-G-A
• chr19-17606132-G-C
• chr19-17606132-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_001080421.3(UNC13A):​c.5034C>T​(p.Asp1678Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,072 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 (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UNC13A NM_001080421.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.431
• Publications: 0 publications found

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]

UNC13A Gene-Disease associations (from GenCC):

• congenital nervous system disorder

  Inheritance: Unknown Classification: LIMITED Submitted by: Illumina, ClinGen

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=-0.59).
• BP6: Variant 19-17606132-G-A is Benign according to our data. Variant chr19-17606132-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3050776.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.431 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080421.3. 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
	UNC13A	NM_001080421.3	MANE Select	c.5034C>T	p.Asp1678Asp	synonymous	Exon 44 of 44	NP_001073890.2	Q9UPW8
	UNC13A	NM_001387021.1		c.5022C>T	p.Asp1674Asp	synonymous	Exon 42 of 42	NP_001373950.1
	UNC13A	NM_001387022.1		c.5019C>T	p.Asp1673Asp	synonymous	Exon 42 of 42	NP_001373951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13A	ENST00000519716.7	TSL:5 MANE Select	c.5034C>T	p.Asp1678Asp	synonymous	Exon 44 of 44	ENSP00000429562.2	Q9UPW8
	UNC13A	ENST00000551649.5	TSL:5	c.5091C>T	p.Asp1697Asp	synonymous	Exon 45 of 45	ENSP00000447236.1	F8W059
	UNC13A	ENST00000552293.5	TSL:5	c.5016C>T	p.Asp1672Asp	synonymous	Exon 42 of 42	ENSP00000447572.1	F8W0P6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1441072 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715750

African (AFR) AF: 0.00 AC: 0 AN: 31432

American (AMR) AF: 0.00 AC: 0 AN: 42796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25470

East Asian (EAS) AF: 0.00 AC: 0 AN: 37800

South Asian (SAS) AF: 0.00 AC: 0 AN: 83524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1103752

Other (OTH) AF: 0.00 AC: 0 AN: 59514

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UNC13A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Uncertain	0.97
PhyloP100		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs890020457; hg19: chr19-17716941;