19-17275816-T-G

Position:

• chr19-17275816-T-G

Variant summary

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

The NM_014173.4(BABAM1):​c.560T>G​(p.Phe187Cys) 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: 32)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99

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, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.560T>G	p.Phe187Cys	missense_variant	6/9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.560T>G	p.Phe187Cys	missense_variant	6/9		NP_001028721.1
BABAM1	NM_001288756.2	c.560T>G	p.Phe187Cys	missense_variant	6/9		NP_001275685.1
BABAM1	NM_001288757.2	c.345-679T>G		intron_variant			NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.560T>G	p.Phe187Cys	missense_variant	6/9	1	NM_014173.4	ENSP00000471605	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2023

The c.560T>G (p.F187C) alteration is located in exon 6 (coding exon 5) of the BABAM1 gene. This alteration results from a T to G substitution at nucleotide position 560, causing the phenylalanine (F) at amino acid position 187 to be replaced by a cysteine (C). 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	0.65
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;T;T;T;T;.;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	.;.;T;D;T;T;D;D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.5	M;M;.;M;.;.;.;.
MutationTaster	Benign	0.81	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.5	.;D;.;.;.;.;.;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0050	.;D;.;.;.;.;.;.
Sift4G	Uncertain	0.016	D;D;T;D;T;D;T;T
Polyphen		0.98	D;D;.;D;.;.;.;.
Vest4		0.84
MutPred		0.56		Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);.;.;.;Gain of helix (P = 0.2294);
MVP		0.63
MPC		1.1
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.67

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: chr19-17386625;