4-143999442-CG-TT

Variant names:

• chr4-143999442-CG-TT
• NM_002100.6:c.143_144delCGinsAA
• GYPB p.Thr48Lys

Variant summary

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

The NM_002100.6(GYPB):​c.143_144delCGinsAA​(p.Thr48Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GYPB NM_002100.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 0 publications found

Genes affected

GYPB (HGNC:4703): (glycophorin B (MNS blood group)) Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. GYPB gene consists of 5 exons and has 97% sequence homology with GYPA from the 5' UTR to the coding sequence encoding the first 45 amino acids. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta; also, Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

GUSBP5 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002100.6. 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
	GYPB	NM_002100.6	MANE Select	c.143_144delCGinsAA	p.Thr48Lys	missense	N/A	NP_002091.4	P06028-1
	GYPB	NM_001304382.1		c.65_66delCGinsAA	p.Thr22Lys	missense	N/A	NP_001291311.1	P06028

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	ENST00000502664.6	TSL:1 MANE Select	c.143_144delCGinsAA	p.Thr48Lys	missense	N/A	ENSP00000427690.1	P06028-1
	GYPB	ENST00000506516.6	TSL:1	c.65_66delCGinsAA	p.Thr22Lys	missense	N/A	ENSP00000424025.2	D6RBP2
	GYPB	ENST00000429670.3	TSL:1	c.143_144delCGinsAA	p.Thr48Lys	missense	N/A	ENSP00000394200.2	E7ERJ5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.96

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-144920595;