9-101362718-T-C

Variant names:

• chr9-101362718-T-C
• rs80356747
• NM_001701.4:c.967A>G

Variant summary

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

The NM_001701.4(BAAT):​c.967A>G​(p.Ile323Val) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BAAT NM_001701.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.405
• Publications: 2 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Laboratory for Molecular Medicine
• bile acid conjugation defect 1

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=0.29962587).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAAT	NM_001701.4	MANE Select	c.967A>G	p.Ile323Val	missense	Exon 4 of 4	NP_001692.1
	BAAT	NM_001127610.2		c.967A>G	p.Ile323Val	missense	Exon 4 of 4	NP_001121082.1
	BAAT	NM_001374715.1		c.967A>G	p.Ile323Val	missense	Exon 4 of 4	NP_001361644.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAAT	ENST00000259407.7	TSL:1 MANE Select	c.967A>G	p.Ile323Val	missense	Exon 4 of 4	ENSP00000259407.2
	BAAT	ENST00000395051.4	TSL:1	c.967A>G	p.Ile323Val	missense	Exon 4 of 4	ENSP00000378491.3
	BAAT	ENST00000674556.1		c.967A>G	p.Ile323Val	missense	Exon 4 of 4	ENSP00000501610.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hemolytic uremic syndrome, atypical, susceptibility to, 1 Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.1
DANN	Benign	0.93
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.41
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.095
Sift	Benign	0.25	T
Sift4G	Benign	0.51	T
Polyphen		0.031	B
Vest4		0.024
MutPred		0.51		Gain of disorder (P = 0.2064)
MVP		0.27
MPC		0.060
ClinPred		0.11	T
GERP RS		3.8
Varity_R		0.065
gMVP		0.19
Mutation Taster		=17/83	disease causing (ClinVar)

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: rs80356747; hg19: chr9-104125000;