19-17274114-G-T

Position:

• chr19-17274114-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014173.4(BABAM1):​c.473G>T​(p.Gly158Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

Genes affected

BABAM1 (HGNC:25008): (BRISC and BRCA1 A complex member 1) Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; positive regulation of DNA repair; and protein K63-linked deubiquitination. Located in cytosol and nuclear body. Part of BRCA1-A complex and BRISC complex. [provided by Alliance of Genome Resources, Apr 2022]

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.473G>T	p.Gly158Val	missense_variant	5/9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.473G>T	p.Gly158Val	missense_variant	5/9		NP_001028721.1
BABAM1	NM_001288756.2	c.473G>T	p.Gly158Val	missense_variant	5/9		NP_001275685.1
BABAM1	NM_001288757.2	c.345-2381G>T		intron_variant			NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.473G>T	p.Gly158Val	missense_variant	5/9	1	NM_014173.4	ENSP00000471605	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2023

The c.473G>T (p.G158V) alteration is located in exon 5 (coding exon 4) of the BABAM1 gene. This alteration results from a G to T substitution at nucleotide position 473, causing the glycine (G) at amino acid position 158 to be replaced by a valine (V). 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	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T;.;T;T;.;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	.;.;D;D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.4	M;M;.;.;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.3	.;D;.;.;.;.;.;.;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0070	.;D;.;.;.;.;.;.;.
Sift4G	Uncertain	0.015	D;D;D;D;D;D;D;D;D
Polyphen		0.99	D;D;.;.;D;.;.;.;.
Vest4		0.86
MutPred		0.41		Loss of disorder (P = 0.0694);Loss of disorder (P = 0.0694);Loss of disorder (P = 0.0694);Loss of disorder (P = 0.0694);Loss of disorder (P = 0.0694);Loss of disorder (P = 0.0694);Loss of disorder (P = 0.0694);.;Loss of disorder (P = 0.0694);
MVP		0.74
MPC		1.1
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.66
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17384923;