Genetic Variant NM_014173.4:c.674A>G (chr19-17276599-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014173.4(BABAM1):c.674A>G(p.Gln225Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q225L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BABAM1
NM_014173.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34382933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4 link	c.674A>G	p.Gln225Arg	missense_variant	Exon 7 of 9	ENST00000598188.6	NP_054892.2	Q9NWV8-1A0A024R7L2
BABAM1	NM_001033549.3 link	c.674A>G	p.Gln225Arg	missense_variant	Exon 7 of 9		NP_001028721.1	Q9NWV8-1A0A024R7L2
BABAM1	NM_001288756.2 link	c.674A>G	p.Gln225Arg	missense_variant	Exon 7 of 9		NP_001275685.1	Q9NWV8-1A0A024R7L2
BABAM1	NM_001288757.2 link	c.449A>G	p.Gln150Arg	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.674A>G	p.Gln225Arg	missense_variant	Exon 7 of 9	1	NM_014173.4	ENSP00000471605.1	Q9NWV8-1
ENSG00000269307	ENST00000596542.1 link	n.*288A>G		non_coding_transcript_exon_variant	Exon 6 of 10	2		ENSP00000469159.2	M0QXG9
ENSG00000269307	ENST00000596542.1 link	n.*288A>G		3_prime_UTR_variant	Exon 6 of 10	2		ENSP00000469159.2	M0QXG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722610

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:

0.00

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

Feb 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.674A>G (p.Q225R) alteration is located in exon 7 (coding exon 6) of the BABAM1 gene. This alteration results from a A to G substitution at nucleotide position 674, causing the glutamine (Q) at amino acid position 225 to be replaced by an arginine (R). 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

0.091

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.056

T;T;T;T;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

.;T;.;T;.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.29

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

M;.;M;M;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

.;.;N;.;.;.

REVEL

Benign

0.072

Sift

Benign

0.10

.;.;T;.;.;.

Sift4G

Benign

0.27

T;T;T;T;T;D

Polyphen

0.61

P;.;P;P;.;.

Vest4

0.63

MutPred

0.19

Gain of phosphorylation at S227 (P = 0.0723);.;Gain of phosphorylation at S227 (P = 0.0723);Gain of phosphorylation at S227 (P = 0.0723);.;Gain of phosphorylation at S227 (P = 0.0723);

MVP

0.50

MPC

0.69

ClinPred

0.77

GERP RS

5.6

Varity_R

0.10

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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