rs1027994578

Variant names:

• chr11-57744616-C-A
• rs1027994578
• NM_001145101.3:c.1657G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-57744616-C-A
• chr11-57744616-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001145101.3(BTBD18):​c.1657G>T​(p.Glu553*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: BTBD18 NM_001145101.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• Publications: 0 publications found

Genes affected

BTBD18 (HGNC:37214): (BTB domain containing 18) Predicted to be involved in several processes, including male gamete generation; piRNA biosynthetic process; and positive regulation of transcription elongation from RNA polymerase II promoter. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254732 (HGNC:):

TMX2-CTNND1 (HGNC:41992): (TMX2-CTNND1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TMX2 (thioredoxin-related transmembrane protein 2) and CTNND1 (catenin, cadherin-associated protein, delta 1) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145101.3. 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
	BTBD18	NM_001145101.3	MANE Select	c.1657G>T	p.Glu553*	stop_gained	Exon 3 of 3	NP_001138573.1	B2RXH4
	TMX2-CTNND1	NR_037646.1		n.346+6948C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD18	ENST00000422652.6	TSL:4 MANE Select	c.1657G>T	p.Glu553*	stop_gained	Exon 3 of 3	ENSP00000394472.1	B2RXH4
	BTBD18	ENST00000436147.3	TSL:1	c.1657G>T	p.Glu553*	stop_gained	Exon 2 of 2	ENSP00000397020.2	B2RXH4
	ENSG00000254732	ENST00000531074.1	TSL:3	n.*152+1632C>A		intron	N/A	ENSP00000457993.1	H3BV83

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399368 Hom.: 0 Cov.: 34 AF XY: 0.00000145 AC XY: 1 AN XY: 690192

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078966

Other (OTH) AF: 0.00 AC: 0 AN: 57998

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Benign	0.46	N
PhyloP100		2.6
Vest4		0.084
GERP RS		5.0
Mutation Taster		=96/104	disease causing

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: rs1027994578; hg19: chr11-57512088;