NM_199191.3:c.398G>A

Variant names:

• chr2-28025323-G-A
• rs138608273
• NM_199191.3:c.398G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_199191.3(BABAM2):​c.398G>A​(p.Arg133Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,612,956 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 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: BABAM2 NM_199191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.24
• Publications: 3 publications found

Genes affected

BABAM2 (HGNC:1106): (BRISC and BRCA1 A complex member 2) This gene encodes an anti-apoptotic, death receptor-associated protein that interacts with tumor necrosis factor-receptor-1. The encoded protein acts as an adapter in several protein complexes, including the BRCA1-A complex and the BRISC complex. The BRCA1-A complex possesses ubiquitinase activity and targets sites of double strand DNA breaks, while the BRISC complex exhibits deubiquitinase activity and is involved in mitotic spindle assembly. This gene is upregulated in several types of cancer. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1774284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199191.3. 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
	BABAM2	NM_199191.3	MANE Select	c.398G>A	p.Arg133Gln	missense	Exon 5 of 12	NP_954661.1	Q9NXR7-2
	BABAM2	NM_001329114.2		c.398G>A	p.Arg133Gln	missense	Exon 5 of 14	NP_001316043.1
	BABAM2	NM_001329115.2		c.398G>A	p.Arg133Gln	missense	Exon 6 of 14	NP_001316044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BABAM2	ENST00000379624.6	TSL:1 MANE Select	c.398G>A	p.Arg133Gln	missense	Exon 5 of 12	ENSP00000368945.1	Q9NXR7-2
	BABAM2	ENST00000342045.6	TSL:1	c.398G>A	p.Arg133Gln	missense	Exon 6 of 13	ENSP00000339371.2	Q9NXR7-2
	BABAM2	ENST00000361704.6	TSL:1	c.398G>A	p.Arg133Gln	missense	Exon 5 of 13	ENSP00000354699.2	Q9NXR7-4

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000599 AC: 15 AN: 250468 AF XY: 0.0000369

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000144 AC: 211 AN: 1460864 Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 106 AN XY: 726806

African (AFR) AF: 0.0000299 AC: 1 AN: 33422

American (AMR) AF: 0.0000900 AC: 4 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000179 AC: 199 AN: 1111720

Other (OTH) AF: 0.000116 AC: 7 AN: 60330

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74278

African (AFR) AF: 0.0000483 AC: 2 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.0000869

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	T
Eigen	Benign	0.078
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		9.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.25
Sift	Benign	0.70	T
Sift4G	Benign	0.37	T
Polyphen		0.94	P
Vest4		0.64
MVP		0.44
MPC		0.51
ClinPred		0.092	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.33
Mutation Taster		=73/27	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: rs138608273; hg19: chr2-28248190; COSMIC: COSV59616782;