Genetic Variant ABCB8:p.His109Tyr (chr7-151033834-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007188.5(ABCB8):c.325C>T(p.His109Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ABCB8
NM_007188.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.92

Publications

0 publications found

Variant links:

Genes affected

ABCB8 (HGNC:49): (ATP binding cassette subfamily B member 8) This nuclear gene encodes a multi-pass membrane protein that is targeted to the mitochondrial inner membrane. The encoded protein is an ATP-dependent transporter that may mediate the passage of organic and inorganic molecules out of the mitochondria. Loss of function of the related gene in mouse results in a disruption of iron homeostasis between the mitochondria and cytosol. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ABCB8 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055661023).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007188.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB8	NM_007188.5	MANE Select	c.325C>T	p.His109Tyr	missense	Exon 2 of 16	NP_009119.2	Q9NUT2-2
ABCB8	NM_001282291.2		c.376C>T	p.His126Tyr	missense	Exon 3 of 17	NP_001269220.1	Q9NUT2-1
ABCB8	NM_001282292.2		c.325C>T	p.His109Tyr	missense	Exon 2 of 16	NP_001269221.1	Q9NUT2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB8	ENST00000358849.9	TSL:1 MANE Select	c.325C>T	p.His109Tyr	missense	Exon 2 of 16	ENSP00000351717.4	Q9NUT2-2
ABCB8	ENST00000498578.5	TSL:1	c.325C>T	p.His109Tyr	missense	Exon 2 of 16	ENSP00000418271.1	Q9NUT2-3
ABCB8	ENST00000879589.1		c.457C>T	p.His153Tyr	missense	Exon 3 of 17	ENSP00000549648.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250218

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.029

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.057

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.54

M_CAP

Benign

0.045

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.0

PhyloP100

-1.9

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.1

REVEL

Benign

0.23

Sift

Benign

0.65

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.11

MutPred

0.39

Loss of disorder (P = 0.0477)

MVP

0.68

MPC

0.25

ClinPred

0.020

GERP RS

-1.9

Varity_R

0.022

gMVP

0.19

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over