6-146654163-C-A

Variant names:

• chr6-146654163-C-A
• rs765380601
• NM_024694.4:c.359C>A

Variant summary

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

The NM_024694.4(ADGB):​c.359C>A​(p.Thr120Lys) 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. T120M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADGB NM_024694.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838
• Publications: 4 publications found

Genes affected

ADGB (HGNC:21212): (androglobin) Predicted to enable calcium-dependent cysteine-type endopeptidase activity; heme binding activity; and oxygen binding activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07867956).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024694.4. 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
	ADGB	NM_024694.4	MANE Select	c.359C>A	p.Thr120Lys	missense	Exon 4 of 36	NP_078970.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGB	ENST00000397944.8	TSL:5 MANE Select	c.359C>A	p.Thr120Lys	missense	Exon 4 of 36	ENSP00000381036.3	Q8N7X0-1
	ADGB	ENST00000493950.6	TSL:1	n.359C>A		non_coding_transcript_exon	Exon 4 of 32	ENSP00000430244.1	E5RGD1
	ADGB	ENST00000681847.1		c.359C>A	p.Thr120Lys	missense	Exon 4 of 36	ENSP00000505524.1	A0A7P0T963

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.045
DANN	Benign	0.17
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.84
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.074
Sift	Benign	0.76	T
Sift4G	Benign	0.88	T
Polyphen		0.32	B
Vest4		0.17
MutPred		0.55		Gain of ubiquitination at T120 (P = 0.0128)
MVP		0.030
ClinPred		0.094	T
GERP RS		-7.4
Varity_R		0.052
gMVP		0.26
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs765380601; hg19: chr6-146975299;