rs147092030

Variant names:

• chr8-24313543-T-C
• rs147092030
• NM_014265.6:c.539T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-24313543-T-C
• chr8-24313543-T-G

Variant summary

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

The NM_014265.6(ADAM28):​c.539T>C​(p.Leu180Ser) 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. 16/22 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. L180W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM28 NM_014265.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 2 publications found

Genes affected

ADAM28 (HGNC:206): (ADAM metallopeptidase domain 28) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene is a lymphocyte-expressed ADAM protein. This gene is present in a gene cluster with other members of the ADAM family on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

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=0.08735475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014265.6. 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
	ADAM28	NM_014265.6	MANE Select	c.539T>C	p.Leu180Ser	missense	Exon 6 of 23	NP_055080.2	Q9UKQ2-1
	ADAM28	NM_001304351.2		c.539T>C	p.Leu180Ser	missense	Exon 6 of 22	NP_001291280.1
	ADAM28	NM_021777.5		c.539T>C	p.Leu180Ser	missense	Exon 6 of 14	NP_068547.2	Q9UKQ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM28	ENST00000265769.9	TSL:1 MANE Select	c.539T>C	p.Leu180Ser	missense	Exon 6 of 23	ENSP00000265769.4	Q9UKQ2-1
	ADAM28	ENST00000437154.6	TSL:1	c.539T>C	p.Leu180Ser	missense	Exon 6 of 14	ENSP00000393699.2	Q9UKQ2-2
	ADAM28	ENST00000699027.1		c.539T>C	p.Leu180Ser	missense	Exon 6 of 24	ENSP00000514095.1	A0A8V8TMM6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.35
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.13
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.052
Sift	Benign	0.47	T
Sift4G	Benign	0.87	T
Polyphen		0.0010	B
Vest4		0.058
MutPred		0.55		Gain of disorder (P = 0.0661)
MVP		0.28
MPC		0.047
ClinPred		0.023	T
GERP RS		0.75
Varity_R		0.026
gMVP		0.39
Mutation Taster		=93/7	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: rs147092030; hg19: chr8-24171056;