19-17274114-G-T

Variant names:

• chr19-17274114-G-T
• NM_014173.4:c.473G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ENSG00000269307 (HGNC:):

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014173.4. 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
	BABAM1	NM_014173.4	MANE Select	c.473G>T	p.Gly158Val	missense	Exon 5 of 9	NP_054892.2	Q9NWV8-1
	BABAM1	NM_001033549.3		c.473G>T	p.Gly158Val	missense	Exon 5 of 9	NP_001028721.1	Q9NWV8-1
	BABAM1	NM_001288756.2		c.473G>T	p.Gly158Val	missense	Exon 5 of 9	NP_001275685.1	Q9NWV8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BABAM1	ENST00000598188.6	TSL:1 MANE Select	c.473G>T	p.Gly158Val	missense	Exon 5 of 9	ENSP00000471605.1	Q9NWV8-1
	BABAM1	ENST00000359435.8	TSL:1	c.473G>T	p.Gly158Val	missense	Exon 5 of 9	ENSP00000352408.3	Q9NWV8-1
	BABAM1	ENST00000602066.5	TSL:1	c.473G>T	p.Gly158Val	missense	Exon 4 of 6	ENSP00000471246.1	M0R0I0

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

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	Pathogenic	0.68
PhyloP100		7.2
Varity_R		0.66
gMVP		0.69
Mutation Taster		=49/51	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-17384923;