19-17276580-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014173.4(BABAM1):c.655C>T(p.Arg219Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000164 in 1,606,610 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: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

BABAM1
NM_014173.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

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:

ENSG00000269307 (HGNC:):

ENSG00000269307 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4 link	c.655C>T	p.Arg219Cys	missense_variant	Exon 7 of 9	ENST00000598188.6	NP_054892.2	Q9NWV8-1A0A024R7L2
BABAM1	NM_001033549.3 link	c.655C>T	p.Arg219Cys	missense_variant	Exon 7 of 9		NP_001028721.1	Q9NWV8-1A0A024R7L2
BABAM1	NM_001288756.2 link	c.655C>T	p.Arg219Cys	missense_variant	Exon 7 of 9		NP_001275685.1	Q9NWV8-1A0A024R7L2
BABAM1	NM_001288757.2 link	c.430C>T	p.Arg144Cys	missense_variant	Exon 4 of 6		NP_001275686.1	Q9NWV8J3KQS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BABAM1	ENST00000598188.6 link	c.655C>T	p.Arg219Cys	missense_variant	Exon 7 of 9	1	NM_014173.4	ENSP00000471605.1	Q9NWV8-1
ENSG00000269307	ENST00000596542.1 link	n.*269C>T		non_coding_transcript_exon_variant	Exon 6 of 10	2		ENSP00000469159.2	M0QXG9
ENSG00000269307	ENST00000596542.1 link	n.*269C>T		3_prime_UTR_variant	Exon 6 of 10	2		ENSP00000469159.2	M0QXG9

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

235448

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

127716

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:

0.000985

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000565

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000176

AC:

256

AN:

1454266

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

146

AN XY:

722586

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:

0.00112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000773

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.655C>T (p.R219C) alteration is located in exon 7 (coding exon 6) of the BABAM1 gene. This alteration results from a C to T substitution at nucleotide position 655, causing the arginine (R) at amino acid position 219 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

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;T;D;D;T;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;.;D;.;D

M_CAP

Benign

0.038

MetaRNN

Pathogenic

0.85

D;D;D;D;D;D

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.8

M;.;M;M;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.9

.;.;D;.;.;.

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

.;.;D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;.;.

Vest4

0.95

MVP

0.71

MPC

1.1

ClinPred

0.95

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.73

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