11-111497391-A-T

Variant names:

• chr11-111497391-A-T
• NM_001367975.1:c.330T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367975.1(BTG4):​c.330T>A​(p.His110Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H110R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTG4 NM_001367975.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0200
• Publications: 0 publications found

Genes affected

BTG4 (HGNC:13862): (BTG anti-proliferation factor 4) 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 can induce G1 arrest in the cell cycle. [provided by RefSeq, Jul 2008]

BTG4 Gene-Disease associations (from GenCC):

• oocyte maturation defect 8

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• female infertility

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12328562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTG4	NM_001367975.1	c.330T>A	p.His110Gln	missense_variant	Exon 4 of 5	ENST00000692032.1	NP_001354904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTG4	ENST00000692032.1	c.330T>A	p.His110Gln	missense_variant	Exon 4 of 5		NM_001367975.1	ENSP00000509850.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.330T>A (p.H110Q) alteration is located in exon 4 (coding exon 3) of the BTG4 gene. This alteration results from a T to A substitution at nucleotide position 330, causing the histidine (H) at amino acid position 110 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.24	T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M;.
PhyloP100		0.020
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.086
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.61	T;T;.
Polyphen		0.47	P;.;.
Vest4		0.092
MutPred		0.55		Gain of ubiquitination at K108 (P = 0.102);Gain of ubiquitination at K108 (P = 0.102);Gain of ubiquitination at K108 (P = 0.102);
MVP		0.32
MPC		0.18
ClinPred		0.37	T
GERP RS		2.7
Varity_R		0.10
gMVP		0.35
Mutation Taster		=95/5	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

hg19: chr11-111368116;