NM_001145101.3:c.1987G>C

Variant names:

• chr11-57744286-C-G
• NM_001145101.3:c.1987G>C

Variant summary

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

The NM_001145101.3(BTBD18):​c.1987G>C​(p.Glu663Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTBD18 NM_001145101.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.735
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064841926).

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.1987G>C	p.Glu663Gln	missense	Exon 3 of 3	NP_001138573.1	B2RXH4
	TMX2-CTNND1	NR_037646.1		n.346+6618C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD18	ENST00000422652.6	TSL:4 MANE Select	c.1987G>C	p.Glu663Gln	missense	Exon 3 of 3	ENSP00000394472.1	B2RXH4
	BTBD18	ENST00000436147.3	TSL:1	c.1987G>C	p.Glu663Gln	missense	Exon 2 of 2	ENSP00000397020.2	B2RXH4
	ENSG00000254732	ENST00000531074.1	TSL:3	n.*152+1302C>G		intron	N/A	ENSP00000457993.1	H3BV83

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.7
DANN	Benign	0.73
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.73
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.048	D
Polyphen		0.041	B
Vest4		0.073
MutPred		0.14		Loss of helix (P = 0.0558)
MVP		0.072
ClinPred		0.10	T
GERP RS		2.2
Varity_R		0.063
gMVP		0.081
Mutation Taster		=97/3	polymorphism

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

hg19: chr11-57511758;