19-17276528-C-G

Variant names:

• chr19-17276528-C-G
• rs765723650
• NM_014173.4:c.603C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014173.4(BABAM1):​c.603C>G​(p.Asn201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• 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: -2.61
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22765112).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014173.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BABAM1	NM_014173.4	MANE Select	c.603C>G	p.Asn201Lys	missense	Exon 7 of 9	NP_054892.2	Q9NWV8-1
	BABAM1	NM_001033549.3		c.603C>G	p.Asn201Lys	missense	Exon 7 of 9	NP_001028721.1	Q9NWV8-1
	BABAM1	NM_001288756.2		c.603C>G	p.Asn201Lys	missense	Exon 7 of 9	NP_001275685.1	Q9NWV8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BABAM1	ENST00000598188.6	TSL:1 MANE Select	c.603C>G	p.Asn201Lys	missense	Exon 7 of 9	ENSP00000471605.1	Q9NWV8-1
	BABAM1	ENST00000359435.8	TSL:1	c.603C>G	p.Asn201Lys	missense	Exon 7 of 9	ENSP00000352408.3	Q9NWV8-1
	BABAM1	ENST00000602066.5	TSL:1	c.603C>G	p.Asn201Lys	missense	Exon 6 of 6	ENSP00000471246.1	M0R0I0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000464 AC: 1 AN: 215694 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.93e-7 AC: 1 AN: 1442080 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715632

African (AFR) AF: 0.00 AC: 0 AN: 32880

American (AMR) AF: 0.0000238 AC: 1 AN: 42014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25746

East Asian (EAS) AF: 0.00 AC: 0 AN: 38310

South Asian (SAS) AF: 0.00 AC: 0 AN: 83072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102750

Other (OTH) AF: 0.00 AC: 0 AN: 59672

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.022
DANN	Benign	0.30
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-2.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.21
Sift	Benign	0.20	T
Sift4G	Benign	0.14	T
Polyphen		0.18	B
Vest4		0.41
MutPred		0.47		Gain of methylation at N201 (P = 0.0033)
MVP		0.48
MPC		0.57
ClinPred		0.26	T
GERP RS		-10
Varity_R		0.18
gMVP		0.35
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs765723650; hg19: chr19-17387337;