chr10-126019719-G-C

Variant names:

• chr10-126019719-G-C
• rs769071080
• NM_001288973.2:c.2636C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001288973.2(ADAM12):​c.2636C>G​(p.Thr879Ser) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM12 NM_001288973.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.58
• Publications: 0 publications found

Genes affected

ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are 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. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05974871).
• BP6: Variant 10-126019719-G-C is Benign according to our data. Variant chr10-126019719-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2256533.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288973.2. 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
	ADAM12	NM_001288973.2	MANE Select	c.2636C>G	p.Thr879Ser	missense	Exon 22 of 23	NP_001275902.1	Q5JRP2
	ADAM12	NM_003474.6		c.2645C>G	p.Thr882Ser	missense	Exon 22 of 23	NP_003465.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	ENST00000448723.2	TSL:5 MANE Select	c.2636C>G	p.Thr879Ser	missense	Exon 22 of 23	ENSP00000391268.2	Q5JRP2
	ADAM12	ENST00000368679.8	TSL:1	c.2645C>G	p.Thr882Ser	missense	Exon 22 of 23	ENSP00000357668.4	O43184-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.065
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.32
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.60	N
PhyloP100		2.6
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.13
Sift	Benign	0.80	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.20		Loss of catalytic residue at T882 (P = 0.0309)
MVP		0.32
MPC		0.20
ClinPred		0.095	T
GERP RS		4.9
Varity_R		0.060
gMVP		0.062
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs769071080; hg19: chr10-127708288;