NM_014173.4:c.837G>T

Variant names:

• chr19-17278895-G-T
• rs8170
• NM_014173.4:c.837G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014173.4(BABAM1):​c.837G>T​(p.Lys279Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32602733).

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.837G>T	p.Lys279Asn	missense	Exon 9 of 9	NP_054892.2	Q9NWV8-1
	BABAM1	NM_001033549.3		c.837G>T	p.Lys279Asn	missense	Exon 9 of 9	NP_001028721.1	Q9NWV8-1
	BABAM1	NM_001288756.2		c.837G>T	p.Lys279Asn	missense	Exon 9 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.837G>T	p.Lys279Asn	missense	Exon 9 of 9	ENSP00000471605.1	Q9NWV8-1
	BABAM1	ENST00000359435.8	TSL:1	c.837G>T	p.Lys279Asn	missense	Exon 9 of 9	ENSP00000352408.3	Q9NWV8-1
	ENSG00000269307	ENST00000596542.1	TSL:2	n.*400+1986G>T		intron	N/A	ENSP00000469159.2	M0QXG9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.0075
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	M
PhyloP100		3.1
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.038
Sift	Benign	0.038	D
Sift4G	Benign	0.30	T
Polyphen		0.53	P
Vest4		0.47
MutPred		0.30		Loss of ubiquitination at K279 (P = 0.0192)
MVP		0.30
MPC		0.60
ClinPred		0.49	T
GERP RS		2.8
Varity_R		0.24
gMVP		0.32
Mutation Taster		=56/44	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: rs8170; hg19: chr19-17389704;