chr19-17268882-C-T

Variant names:

• chr19-17268882-C-T
• rs2073802959
• NM_014173.4:c.76C>T

Variant summary

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

The NM_014173.4(BABAM1):​c.76C>T​(p.Arg26Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000877 in 1,596,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58

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=0.22751912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.76C>T	p.Arg26Cys	missense_variant	Exon 2 of 9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.76C>T	p.Arg26Cys	missense_variant	Exon 2 of 9		NP_001028721.1
BABAM1	NM_001288756.2	c.76C>T	p.Arg26Cys	missense_variant	Exon 2 of 9		NP_001275685.1
BABAM1	NM_001288757.2	c.76C>T	p.Arg26Cys	missense_variant	Exon 2 of 6		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.76C>T	p.Arg26Cys	missense_variant	Exon 2 of 9	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.76C>T		non_coding_transcript_exon_variant	Exon 2 of 10	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD4 exome AF: 0.00000831 AC: 12 AN: 1444116 Hom.: 0 Cov.: 31 AF XY: 0.00000698 AC XY: 5 AN XY: 716770

Gnomad4 AFR exome AF: 0.0000605

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000516

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000634

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74338

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000371 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76C>T (p.R26C) alteration is located in exon 2 (coding exon 1) of the BABAM1 gene. This alteration results from a C to T substitution at nucleotide position 76, causing the arginine (R) at amino acid position 26 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	Benign	0.11
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.068	T;T;T;T;.;T;T;.;T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.062
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	.;D;.;D;D;D;D;D;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.2	M;.;M;.;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	.;N;N;.;.;.;.;.;.;.;.
REVEL	Benign	0.10
Sift	Uncertain	0.0020	.;D;D;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.0030	B;.;B;.;.;B;.;.;.;.;.
Vest4		0.46
MVP		0.21
MPC		1.0
ClinPred		0.94	D
GERP RS		3.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.27
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs2073802959; hg19: chr19-17379691;