chr9-101371346-C-G

Variant names:

• chr9-101371346-C-G
• rs1572983
• NM_001701.4:c.59G>C

Variant summary

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

The NM_001701.4(BAAT):​c.59G>C​(p.Arg20Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R20Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BAAT NM_001701.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42
• Publications: 30 publications found

Genes affected

BAAT (HGNC:932): (bile acid-CoA:amino acid N-acyltransferase) The protein encoded by this gene is a liver enzyme that catalyzes the transfer of C24 bile acids from the acyl-CoA thioester to either glycine or taurine, the second step in the formation of bile acid-amino acid conjugates. The bile acid conjugates then act as a detergent in the gastrointestinal tract, which enhances lipid and fat-soluble vitamin absorption. Defects in this gene are a cause of familial hypercholanemia (FHCA). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

BAAT Gene-Disease associations (from GenCC):

• hypercholanemia, familial 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• bile acid CoA:amino acid N-acyltransferase deficiency

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• familial hypercholanemia

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Laboratory for Molecular Medicine, Orphanet
• bile acid conjugation defect 1

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001701.4. 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
	BAAT	NM_001701.4	MANE Select	c.59G>C	p.Arg20Pro	missense	Exon 2 of 4	NP_001692.1	Q14032
	BAAT	NM_001127610.2		c.59G>C	p.Arg20Pro	missense	Exon 2 of 4	NP_001121082.1	Q14032
	BAAT	NM_001374715.1		c.59G>C	p.Arg20Pro	missense	Exon 2 of 4	NP_001361644.1	Q14032

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAAT	ENST00000259407.7	TSL:1 MANE Select	c.59G>C	p.Arg20Pro	missense	Exon 2 of 4	ENSP00000259407.2	Q14032
	BAAT	ENST00000395051.4	TSL:1	c.59G>C	p.Arg20Pro	missense	Exon 2 of 4	ENSP00000378491.3	Q14032
	BAAT	ENST00000674556.1		c.59G>C	p.Arg20Pro	missense	Exon 2 of 4	ENSP00000501610.1	Q14032

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.0054	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.071	N
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-3.4
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.37
Sift	Benign	0.12	T
Sift4G	Benign	0.21	T
Polyphen		0.98	D
Vest4		0.48
MutPred		0.41		Loss of sheet (P = 0.0817)
MVP		0.71
MPC		0.31
ClinPred		0.72	D
GERP RS		-3.9
Varity_R		0.95
gMVP		0.79
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1572983; hg19: chr9-104133628;