X-75053477-G-T

Position:

• chrX-75053477-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001271696.3(ABCB7):​c.2152C>A​(p.Pro718Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,626 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 2 hem.)
• Consequence: ABCB7 NM_001271696.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

Genes affected

ABCB7 (HGNC:48): (ATP binding cassette subfamily B member 7) The membrane-associated 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 MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a half-transporter involved in the transport of heme from the mitochondria to the cytosol. With iron/sulfur cluster precursors as its substrates, this protein may play a role in metal homeostasis. Mutations in this gene have been associated with mitochondrial iron accumulation and isodicentric (X)(q13) and sideroblastic anemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040244043).
• BP6: Variant X-75053477-G-T is Benign according to our data. Variant chrX-75053477-G-T is described in ClinVar as [Benign]. Clinvar id is 2179355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB7	NM_001271696.3	c.2152C>A	p.Pro718Thr	missense_variant	16/16	ENST00000373394.8	NP_001258625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB7	ENST00000373394.8	c.2152C>A	p.Pro718Thr	missense_variant	16/16	1	NM_001271696.3	ENSP00000362492.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1097626 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 363004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000994

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.8
DANN	Benign	0.22
DEOGEN2	Benign	0.23	.;.;.;T;T;.
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.59	.;T;T;T;T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.040	T;T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.90	.;.;.;L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.070	.;N;N;N;.;N
REVEL	Benign	0.13
Sift	Benign	0.60	.;T;T;T;.;T
Sift4G	Benign	0.47	.;T;T;T;T;T
Polyphen		0.0	B;B;.;B;.;.
Vest4		0.065, 0.11, 0.062, 0.11
MutPred		0.25		.;.;.;Gain of MoRF binding (P = 0.0418);.;.;
MVP		0.51
MPC		1.2
ClinPred		0.027	T
GERP RS		-5.0
Varity_R		0.044
gMVP		0.71

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

LitVar

Other links and lift over

dbSNP: rs752787356; hg19: chrX-74273312;