Variant 19-17269060-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014173.4(BABAM1):c.254G>A(p.Arg85Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,606,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

BABAM1
NM_014173.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.26

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17662853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BABAM1	NM_014173.4 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/9		NP_001028721.1
BABAM1	NM_001288756.2 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/9		NP_001275685.1
BABAM1	NM_001288757.2 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/6		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/9	1	NM_014173.4	ENSP00000471605	P1	Q9NWV8-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

235386

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128368

show subpopulations

Gnomad AFR exome

AF:

0.0000727

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000951

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1454286

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722780

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000454

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:

0.00000271

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000331

AC:

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

Jun 16, 2023

The c.254G>A (p.R85Q) alteration is located in exon 2 (coding exon 1) of the BABAM1 gene. This alteration results from a G to A substitution at nucleotide position 254, causing the arginine (R) at amino acid position 85 to be replaced by a glutamine (Q). 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

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.082

T;T;T;T;.;T;T;.;T;.;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

.;D;.;D;D;D;D;D;.;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.1

M;.;M;.;.;M;.;.;.;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.3

.;N;N;.;.;.;.;.;.;.;.

REVEL

Benign

0.29

Sift

Benign

0.031

.;D;D;.;.;.;.;.;.;.;.

Sift4G

Benign

0.073

T;D;T;D;D;T;D;D;D;D;D

Polyphen

0.88

P;.;P;.;.;P;.;.;.;.;.

Vest4

0.43

MutPred

0.31

Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);Gain of glycosylation at T86 (P = 0.1049);.;Gain of glycosylation at T86 (P = 0.1049);

MVP

0.41

MPC

0.72

ClinPred

0.54

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over