7-20643631-G-T

Variant names:

• chr7-20643631-G-T
• rs757579249
• NM_001163941.2:c.677G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001163941.2(ABCB5):​c.677G>T​(p.Arg226Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCB5 NM_001163941.2 missense, splice_region
• Scores: Splicing: ADA: 0.0001114
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.190
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163941.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	NM_001163941.2	MANE Select	c.677G>T	p.Arg226Met	missense splice_region	Exon 7 of 28	NP_001157413.1	Q2M3G0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.677G>T	p.Arg226Met	missense splice_region	Exon 7 of 28	ENSP00000384881.2	Q2M3G0-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.3
DANN	Benign	0.92
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.46	T
PhyloP100		0.19
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.25
Sift	Benign	0.044	D
Sift4G	Benign	0.15	T
Vest4		0.43
MutPred		0.69		Loss of methylation at R226 (P = 0.0151)
MVP		0.70
MPC		0.0082
ClinPred		0.053	T
GERP RS		-0.14
Varity_R		0.071
gMVP		0.54
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0040
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

Other links and lift over

dbSNP: rs757579249; hg19: chr7-20683254;