7-20632071-A-G

Position:

• chr7-20632071-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001163941.2(ABCB5):​c.272A>G​(p.Asn91Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49

Genes affected

ABCB5 (HGNC:46): (ATP binding cassette subfamily B member 5) ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005 [PubMed 15760339]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity ABCB5_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24441308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.272A>G	p.Asn91Ser	missense_variant	5/28	ENST00000404938.7	NP_001157413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.272A>G	p.Asn91Ser	missense_variant	5/28	1	NM_001163941.2	ENSP00000384881.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1370500 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 676456

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2023

The c.272A>G (p.N91S) alteration is located in exon 5 (coding exon 4) of the ABCB5 gene. This alteration results from a A to G substitution at nucleotide position 272, causing the asparagine (N) at amino acid position 91 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.67	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.20
Sift	Benign	0.29	T
Sift4G	Benign	0.49	T
Vest4		0.17
MutPred		0.42		Gain of disorder (P = 0.0824);
MVP		0.64
MPC		0.0077
ClinPred		0.28	T
GERP RS		4.1
Varity_R		0.050
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-20671694;