11-67995819-G-T

Variant names:

• chr11-67995819-G-T
• rs200930438
• NM_030930.4:c.1155C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030930.4(UNC93B1):​c.1155C>A​(p.Gly385Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,536 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. G385G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: UNC93B1 NM_030930.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4	c.1155C>A	p.Gly385Gly	synonymous_variant	Exon 9 of 11	ENST00000227471.7	NP_112192.2
UNC93B1	XM_011545290.1	c.744C>A	p.Gly248Gly	synonymous_variant	Exon 7 of 9		XP_011543592.1
UNC93B1	XM_011545291.3	c.600C>A	p.Gly200Gly	synonymous_variant	Exon 6 of 8		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1155C>A	p.Gly385Gly	synonymous_variant	Exon 9 of 11	1	NM_030930.4	ENSP00000227471.3
UNC93B1	ENST00000525368.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393536 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 687274

African (AFR) AF: 0.00 AC: 0 AN: 31504

American (AMR) AF: 0.00 AC: 0 AN: 35598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25060

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.00 AC: 0 AN: 79006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1078052

Other (OTH) AF: 0.00 AC: 0 AN: 57732

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.16
DANN	Benign	0.83
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200930438; hg19: chr11-67763290;