7-20628748-G-C

Variant names:

• chr7-20628748-G-C
• rs774669156
• NM_001163941.2:c.169G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163941.2(ABCB5):​c.169G>C​(p.Val57Leu) 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. 16/21 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. V57I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1351533).

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.169G>C	p.Val57Leu	missense	Exon 4 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.169G>C	p.Val57Leu	missense	Exon 4 of 28	ENSP00000384881.2	Q2M3G0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248442 AF XY: 0.00000741

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000830 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.4
DANN	Benign	0.87
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.83	T
PhyloP100		-0.78
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.14
Sift	Benign	0.43	T
Sift4G	Benign	0.75	T
Vest4		0.23
MutPred		0.53		Loss of catalytic residue at V57 (P = 0.5229)
MVP		0.61
MPC		0.0074
ClinPred		0.017	T
GERP RS		-0.91
Varity_R		0.081
gMVP		0.31
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs774669156; hg19: chr7-20668371;