ENST00000339775.10:c.424G>A

Variant names:

• chr21-17604164-C-T
• rs1242564443
• ENST00000339775.10:c.424G>A

Variant summary

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

The ENST00000339775.10(BTG3):​c.424G>A​(p.Ala142Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BTG3 ENST00000339775.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.606
• Publications: 0 publications found

Genes affected

BTG3 (HGNC:1132): (BTG anti-proliferation factor 3) The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein might play a role in neurogenesis in the central nervous system. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

CXADR (HGNC:2559): (CXADR Ig-like cell adhesion molecule) The protein encoded by this gene is a type I membrane receptor for group B coxsackieviruses and subgroup C adenoviruses. Several transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene are found on chromosomes 15, 18, and 21. [provided by RefSeq, May 2011]

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=0.061760187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000339775.10. 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
	BTG3	NM_006806.5	MANE Select	c.311+696G>A		intron	N/A	NP_006797.3
	BTG3	NM_001130914.2		c.424G>A	p.Ala142Thr	missense	Exon 4 of 6	NP_001124386.1	Q14201-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTG3	ENST00000339775.10	TSL:1	c.424G>A	p.Ala142Thr	missense	Exon 4 of 6	ENSP00000344609.6	Q14201-2
	BTG3	ENST00000348354.7	TSL:1 MANE Select	c.311+696G>A		intron	N/A	ENSP00000284879.8	Q14201-1
	BTG3	ENST00000932924.1		c.448G>A	p.Ala150Thr	missense	Exon 4 of 6	ENSP00000602983.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1125306 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 551902

African (AFR) AF: 0.00 AC: 0 AN: 21506

American (AMR) AF: 0.00 AC: 0 AN: 22052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14674

East Asian (EAS) AF: 0.00 AC: 0 AN: 10606

South Asian (SAS) AF: 0.00 AC: 0 AN: 72882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 911068

Other (OTH) AF: 0.00 AC: 0 AN: 40360

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

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	0.25
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.3
DANN	Benign	0.97
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PROVEAN	Benign	0.13	N
REVEL	Benign	0.014
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.17	T
Polyphen		0.086	B
Vest4		0.13
MutPred		0.22		Gain of sheet (P = 0.0477)
MVP		0.043
MPC		1.2
ClinPred		0.21	T
GERP RS		-0.53
gMVP		0.044
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1242564443; hg19: chr21-18976482;