19-17268749-C-G

Variant names:

• chr19-17268749-C-G
• rs10424178
• ENST00000602066.5:c.-58C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000602066.5(BABAM1):​c.-58C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,355,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: BABAM1 ENST00000602066.5 5_prime_UTR
• Scores: Splicing: ADA: 0.9971
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.-13-45C>G		intron_variant	Intron 1 of 8	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.-51-7C>G		splice_region_variant, intron_variant	Intron 1 of 8		NP_001028721.1
BABAM1	NM_001288756.2	c.-13-45C>G		intron_variant	Intron 1 of 8		NP_001275685.1
BABAM1	NM_001288757.2	c.-51-7C>G		splice_region_variant, intron_variant	Intron 1 of 5		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.-13-45C>G		intron_variant	Intron 1 of 8	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.-13-45C>G		intron_variant	Intron 1 of 9	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000221 AC: 3 AN: 1355538 Hom.: 0 Cov.: 30 AF XY: 0.00000151 AC XY: 1 AN XY: 664106

African (AFR) AF: 0.00 AC: 0 AN: 30450

American (AMR) AF: 0.00 AC: 0 AN: 30470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20764

East Asian (EAS) AF: 0.00 AC: 0 AN: 37754

South Asian (SAS) AF: 0.00 AC: 0 AN: 71432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.00000282 AC: 3 AN: 1062020

Other (OTH) AF: 0.00 AC: 0 AN: 56056

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.59
PhyloP100		-0.32
PromoterAI		-0.0090	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.91
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10424178; hg19: chr19-17379558;