19-17276528-C-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014173.4(BABAM1):c.603C>A(p.Asn201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,594,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

BABAM1
NM_014173.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.61

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056380153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4 link	c.603C>A	p.Asn201Lys	missense_variant	Exon 7 of 9	ENST00000598188.6	NP_054892.2	Q9NWV8-1A0A024R7L2
BABAM1	NM_001033549.3 link	c.603C>A	p.Asn201Lys	missense_variant	Exon 7 of 9		NP_001028721.1	Q9NWV8-1A0A024R7L2
BABAM1	NM_001288756.2 link	c.603C>A	p.Asn201Lys	missense_variant	Exon 7 of 9		NP_001275685.1	Q9NWV8-1A0A024R7L2
BABAM1	NM_001288757.2 link	c.378C>A	p.Asn126Lys	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.603C>A	p.Asn201Lys	missense_variant	Exon 7 of 9	1	NM_014173.4	ENSP00000471605.1	Q9NWV8-1
ENSG00000269307	ENST00000596542.1 link	n.*217C>A		non_coding_transcript_exon_variant	Exon 6 of 10	2		ENSP00000469159.2	M0QXG9
ENSG00000269307	ENST00000596542.1 link	n.*217C>A		3_prime_UTR_variant	Exon 6 of 10	2		ENSP00000469159.2	M0QXG9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

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:

0.0000649

AC:

AN:

215694

Hom.:

AF XY:

0.0000514

AC XY:

AN XY:

116788

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000895

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000693

AC:

AN:

1442080

Hom.:

Cov.:

AF XY:

0.00000838

AC XY:

AN XY:

715632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000261

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000580

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.603C>A (p.N201K) alteration is located in exon 7 (coding exon 6) of the BABAM1 gene. This alteration results from a C to A substitution at nucleotide position 603, causing the asparagine (N) at amino acid position 201 to be replaced by a lysine (K). 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

0.53

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.034

DANN

Benign

0.30

DEOGEN2

Benign

0.073

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.014

MetaRNN

Benign

0.056

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

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.4

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

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.21

Sift

Benign

0.20

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

Sift4G

Benign

0.14

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

Polyphen

0.18

B;.;B;B;.;.;.;.

Vest4

0.41

MutPred

0.47

Gain of methylation at N201 (P = 0.0033);.;Gain of methylation at N201 (P = 0.0033);Gain of methylation at N201 (P = 0.0033);.;.;.;Gain of methylation at N201 (P = 0.0033);

MVP

0.48

MPC

0.57

ClinPred

0.18

GERP RS

-10

Varity_R

0.18

gMVP

0.35

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