rs112012170

Variant names:

• chr2-206445465-T-A
• rs112012170
• NM_003812.4:c.373T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-206445465-T-A
• chr2-206445465-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003812.4(ADAM23):​c.373T>A​(p.Ser125Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. S125A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM23 NM_003812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83

Genes affected

ADAM23 (HGNC:202): (ADAM metallopeptidase domain 23) 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. It is reported that inactivation of this gene is associated with tumorigenesis in human cancers. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4070116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.373T>A	p.Ser125Thr	missense_variant	Exon 2 of 26	ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.373T>A	p.Ser125Thr	missense_variant	Exon 2 of 26		NP_001397914.1
ADAM23	XM_005246932.4	c.373T>A	p.Ser125Thr	missense_variant	Exon 2 of 25		XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.373T>A	p.Ser125Thr	missense_variant	Exon 2 of 26	1	NM_003812.4	ENSP00000264377.3
ADAM23	ENST00000374415.7	c.373T>A	p.Ser125Thr	missense_variant	Exon 2 of 26	5		ENSP00000363536.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.15
Sift	Benign	0.21	T;T
Sift4G	Benign	0.094	T;T
Polyphen		0.93	P;.
Vest4		0.49
MutPred		0.38		Loss of disorder (P = 0.0986);Loss of disorder (P = 0.0986);
MVP		0.38
MPC		0.29
ClinPred		0.94	D
GERP RS		4.8
Varity_R		0.10
gMVP		0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs112012170; hg19: chr2-207310189;