19-17275810-G-A

Variant names:

• chr19-17275810-G-A
• rs754324944
• NM_014173.4:c.554G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014173.4(BABAM1):​c.554G>A​(p.Gly185Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.45

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]

ENSG00000269307 (HGNC:):

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.15062115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.554G>A	p.Gly185Glu	missense_variant	Exon 6 of 9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.554G>A	p.Gly185Glu	missense_variant	Exon 6 of 9		NP_001028721.1
BABAM1	NM_001288756.2	c.554G>A	p.Gly185Glu	missense_variant	Exon 6 of 9		NP_001275685.1
BABAM1	NM_001288757.2	c.345-685G>A		intron_variant	Intron 3 of 5		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.554G>A	p.Gly185Glu	missense_variant	Exon 6 of 9	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.*168G>A		non_coding_transcript_exon_variant	Exon 5 of 10	2		ENSP00000469159.2
ENSG00000269307	ENST00000596542.1	n.*168G>A		3_prime_UTR_variant	Exon 5 of 10	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249256 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461576 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

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.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.554G>A (p.G185E) alteration is located in exon 6 (coding exon 5) of the BABAM1 gene. This alteration results from a G to A substitution at nucleotide position 554, causing the glycine (G) at amino acid position 185 to be replaced by a glutamic acid (E). 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	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T;T;T;T;T;.;.;.
Eigen	Benign	-0.071
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	.;.;D;D;T;T;D;D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	M;M;.;M;.;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.27	.;N;.;.;.;.;.;.
REVEL	Benign	0.056
Sift	Benign	0.22	.;T;.;.;.;.;.;.
Sift4G	Benign	1.0	T;T;T;T;T;T;D;T
Polyphen		0.10	B;B;.;B;.;.;.;.
Vest4		0.61
MutPred		0.35		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;.;.;Gain of relative solvent accessibility (P = 0.09);
MVP		0.31
MPC		0.55
ClinPred		0.13	T
GERP RS		4.5
Varity_R		0.27
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs754324944; hg19: chr19-17386619; COSMIC: COSV63920877; COSMIC: COSV63920877;