2-43814506-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022436.3(ABCG5):c.1733A>C(p.Asn578Thr) variant causes a missense change. 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. N578S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCG5 NM_022436.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23

Genes affected

ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

DYNC2LI1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG5	NM_022436.3	c.1733A>C	p.Asn578Thr	missense_variant	12/13	ENST00000405322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG5	ENST00000405322.8	c.1733A>C	p.Asn578Thr	missense_variant	12/13	1	NM_022436.3	P1
ABCG5	ENST00000486512.5	n.2254A>C		non_coding_transcript_exon_variant	8/9	1
ABCG5	ENST00000409962.1	n.2016A>C		non_coding_transcript_exon_variant	8/9	2
ABCG5	ENST00000644754.1	n.2117A>C		non_coding_transcript_exon_variant	9/10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.61	D;D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Uncertain	0.35
Sift	Benign	0.33	T;.
Sift4G	Benign	0.40	T;.
Polyphen		0.62	P;P
Vest4		0.38
MutPred		0.66		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.87
MPC		0.36
ClinPred		0.95	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.59
gMVP		0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-44041645;