Variant 19-17276560-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014173.4(BABAM1):c.635G>C(p.Arg212Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

BABAM1
NM_014173.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.09

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BABAM1	NM_014173.4 linkuse as main transcript	c.635G>C	p.Arg212Pro	missense_variant	7/9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3 linkuse as main transcript	c.635G>C	p.Arg212Pro	missense_variant	7/9		NP_001028721.1
BABAM1	NM_001288756.2 linkuse as main transcript	c.635G>C	p.Arg212Pro	missense_variant	7/9		NP_001275685.1
BABAM1	NM_001288757.2 linkuse as main transcript	c.410G>C	p.Arg137Pro	missense_variant	4/6		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6 linkuse as main transcript	c.635G>C	p.Arg212Pro	missense_variant	7/9	1	NM_014173.4	ENSP00000471605	P1	Q9NWV8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000429

AC:

AN:

233262

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126464

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000952

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452886

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721748

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:

0.00000361

Gnomad4 OTH exome

AF:

0.00

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

May 08, 2023

The c.635G>C (p.R212P) alteration is located in exon 7 (coding exon 6) of the BABAM1 gene. This alteration results from a G to C substitution at nucleotide position 635, causing the arginine (R) at amino acid position 212 to be replaced by a proline (P). 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

1.0

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

D;T;D;D;T;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;D;.;D;.;D

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.8

M;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.9

.;.;D;.;.;.

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

.;.;D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;.;.

Vest4

0.97

MutPred

0.86

Gain of glycosylation at T213 (P = 0.0181);.;Gain of glycosylation at T213 (P = 0.0181);Gain of glycosylation at T213 (P = 0.0181);.;Gain of glycosylation at T213 (P = 0.0181);

MVP

0.84

MPC

1.2

ClinPred

0.99

GERP RS

4.6

Varity_R

0.97

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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