19-17276580-C-A

Variant names:

• chr19-17276580-C-A
• NM_014173.4:c.655C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014173.4(BABAM1):​c.655C>A​(p.Arg219Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R219C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.17

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.655C>A	p.Arg219Ser	missense_variant	Exon 7 of 9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.655C>A	p.Arg219Ser	missense_variant	Exon 7 of 9		NP_001028721.1
BABAM1	NM_001288756.2	c.655C>A	p.Arg219Ser	missense_variant	Exon 7 of 9		NP_001275685.1
BABAM1	NM_001288757.2	c.430C>A	p.Arg144Ser	missense_variant	Exon 4 of 6		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.655C>A	p.Arg219Ser	missense_variant	Exon 7 of 9	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.*269C>A		non_coding_transcript_exon_variant	Exon 6 of 10	2		ENSP00000469159.2
ENSG00000269307	ENST00000596542.1	n.*269C>A		3_prime_UTR_variant	Exon 6 of 10	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454266 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000229

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;T;D;D;T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D;.;D;.;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D
MetaSVM	Uncertain	0.044	D
MutationAssessor	Uncertain	2.8	M;.;M;M;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.2	.;.;D;.;.;.
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0030	.;.;D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	D;.;D;D;.;.
Vest4		0.96
MutPred		0.79		Gain of glycosylation at R219 (P = 0.0256);.;Gain of glycosylation at R219 (P = 0.0256);Gain of glycosylation at R219 (P = 0.0256);.;Gain of glycosylation at R219 (P = 0.0256);
MVP		0.73
MPC		1.0
ClinPred		0.99	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.80

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.

Other links and lift over

hg19: chr19-17387389;