Variant chr19-17278845-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014173.4(BABAM1):c.787G>A(p.Asp263Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BABAM1
NM_014173.4 missense, splice_region

Scores

Splicing: ADA: 0.9996

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.11

Variant links:

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]

BABAM1 links:

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

USHBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BABAM1	NM_014173.4 linkuse as main transcript	c.787G>A	p.Asp263Asn	missense_variant, splice_region_variant	9/9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3 linkuse as main transcript	c.787G>A	p.Asp263Asn	missense_variant, splice_region_variant	9/9		NP_001028721.1
BABAM1	NM_001288756.2 linkuse as main transcript	c.787G>A	p.Asp263Asn	missense_variant, splice_region_variant	9/9		NP_001275685.1
BABAM1	NM_001288757.2 linkuse as main transcript	c.562G>A	p.Asp188Asn	missense_variant, splice_region_variant	6/6		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6 linkuse as main transcript	c.787G>A	p.Asp263Asn	missense_variant, splice_region_variant	9/9	1	NM_014173.4	ENSP00000471605	P1	Q9NWV8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459602

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 25, 2024

The c.787G>A (p.D263N) alteration is located in exon 9 (coding exon 8) of the BABAM1 gene. This alteration results from a G to A substitution at nucleotide position 787, causing the aspartic acid (D) at amino acid position 263 to be replaced by an asparagine (N). 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

-0.0098

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.068

T;T;T;T;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

.;D;.;D;.

M_CAP

Benign

0.024

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.4

M;.;M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.9

.;.;N;.;.

REVEL

Benign

0.19

Sift

Uncertain

0.0080

.;.;D;.;.

Sift4G

Uncertain

0.053

T;D;T;T;D

Polyphen

0.0080

B;.;B;B;.

Vest4

0.44

MutPred

0.49

Loss of phosphorylation at S260 (P = 0.1307);.;Loss of phosphorylation at S260 (P = 0.1307);Loss of phosphorylation at S260 (P = 0.1307);.;

MVP

0.52

MPC

0.28

ClinPred

0.85

GERP RS

5.1

Varity_R

0.24

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over