NM_030930.4:c.87C>A

Variant names:

• chr11-68003957-G-T
• rs937751489
• NM_030930.4:c.87C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_030930.4(UNC93B1):​c.87C>A​(p.Pro29Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000969 in 1,238,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P29P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: UNC93B1 NM_030930.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886
• Publications: 0 publications found

Genes affected

UNC93B1 (HGNC:13481): (unc-93 homolog B1, TLR signaling regulator) This gene encodes a protein that is involved in innate and adaptive immune response by regulating toll-like receptor signaling. The encoded protein traffics nucleotide sensing toll-like receptors to the endolysosome from the endoplasmic reticulum. Deficiency of the encoded protein has been associated with herpes simplex encephalitis. [provided by RefSeq, Feb 2014]

UNC93B1 Gene-Disease associations (from GenCC):

• herpes simplex encephalitis, susceptibility to, 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000309414 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.886 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4	c.87C>A	p.Pro29Pro	synonymous_variant	Exon 1 of 11	ENST00000227471.7	NP_112192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7	c.87C>A	p.Pro29Pro	synonymous_variant	Exon 1 of 11	1	NM_030930.4	ENSP00000227471.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000969 AC: 12 AN: 1238658 Hom.: 0 Cov.: 32 AF XY: 0.0000132 AC XY: 8 AN XY: 607812

African (AFR) AF: 0.00 AC: 0 AN: 25608

American (AMR) AF: 0.00 AC: 0 AN: 22914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21050

East Asian (EAS) AF: 0.00 AC: 0 AN: 26504

South Asian (SAS) AF: 0.0000835 AC: 5 AN: 59878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3566

European-Non Finnish (NFE) AF: 0.00000700 AC: 7 AN: 1000288

Other (OTH) AF: 0.00 AC: 0 AN: 50132

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		-0.89
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs937751489; hg19: chr11-67771427;