Genetic Variant NM_022169.5:c.68C>T (chr11-119150033-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022169.5(ABCG4):c.68C>T(p.Thr23Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. T23K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ABCG4
NM_022169.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.825

Publications

2 publications found

Variant links:

Genes affected

ABCG4 (HGNC:13884): (ATP binding cassette subfamily G member 4) The protein encoded by this gene is a member of the ATP-binding cassette (ABC) transporter superfamily. 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). The encoded protein is a member of the White subfamily and plays an important role in cellular cholesterol homeostasis. This protein functions as either a homodimer or as a heterodimer with another ABC subfamily protein such as ABCG1. [provided by RefSeq, Jan 2017]

ABCG4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16005069).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022169.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCG4	NM_022169.5	MANE Select	c.68C>T	p.Thr23Met	missense	Exon 2 of 15	NP_071452.2
ABCG4	NM_001348192.2		c.-171C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 16	NP_001335121.1	Q9H172-2
ABCG4	NM_001142505.1		c.68C>T	p.Thr23Met	missense	Exon 2 of 15	NP_001135977.1	Q9H172-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCG4	ENST00000619701.5	TSL:1 MANE Select	c.68C>T	p.Thr23Met	missense	Exon 2 of 15	ENSP00000481728.1	Q9H172-1
ABCG4	ENST00000622721.1	TSL:1	c.68C>T	p.Thr23Met	missense	Exon 1 of 14	ENSP00000484289.1	Q9H172-1
ABCG4	ENST00000615496.4	TSL:2	c.68C>T	p.Thr23Met	missense	Exon 2 of 15	ENSP00000479253.1	Q9H172-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250386

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.12

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.77

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

0.82

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.56

REVEL

Benign

0.046

Sift

Uncertain

0.012

Sift4G

Uncertain

0.057

Polyphen

0.92

Vest4

0.18

MutPred

0.43

Loss of phosphorylation at T23 (P = 0.0597)

MVP

0.56

ClinPred

0.27

GERP RS

0.52

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.035

gMVP

0.36

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over