chr11-111495253-A-C

Variant names:

• chr11-111495253-A-C
• NM_001367975.1:c.572T>G

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.572T>G​(p.Val191Gly) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTG4 NM_001367975.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.658
• 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=0.07793993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTG4	NM_001367975.1	c.572T>G	p.Val191Gly	missense_variant	Exon 5 of 5	ENST00000692032.1	NP_001354904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTG4	ENST00000692032.1	c.572T>G	p.Val191Gly	missense_variant	Exon 5 of 5		NM_001367975.1	ENSP00000509850.1
BTG4	ENST00000689553.1	c.572T>G	p.Val191Gly	missense_variant	Exon 7 of 7			ENSP00000508793.1
BTG4	ENST00000356018.6	c.572T>G	p.Val191Gly	missense_variant	Exon 5 of 6	5		ENSP00000348300.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.572T>G (p.V191G) alteration is located in exon 5 (coding exon 4) of the BTG4 gene. This alteration results from a T to G substitution at nucleotide position 572, causing the valine (V) at amino acid position 191 to be replaced by a glycine (G). 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	0.065
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.042
DANN	Benign	0.49
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.66
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.049
Sift	Benign	0.071	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.078
MutPred		0.38		Loss of stability (P = 0.0133);
MVP		0.51
MPC		0.23
ClinPred		0.16	T
GERP RS		-8.8
Varity_R		0.041
gMVP		0.14
Mutation Taster		=95/5	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: chr11-111365978;