rs149165152

Variant names:

• chr2-206445453-A-C
• rs149165152
• NM_003812.4:c.361A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-206445453-A-C
• chr2-206445453-A-G
• chr2-206445453-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003812.4(ADAM23):​c.361A>C​(p.Ile121Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000802 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (1 hom.)
• Consequence: ADAM23 NM_003812.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032050163).
• BS2: High AC in GnomAd4 at 60 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003812.4. 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
	ADAM23	NM_003812.4	MANE Select	c.361A>C	p.Ile121Leu	missense	Exon 2 of 26	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.361A>C	p.Ile121Leu	missense	Exon 2 of 26	NP_001397914.1	E7EWD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM23	ENST00000264377.8	TSL:1 MANE Select	c.361A>C	p.Ile121Leu	missense	Exon 2 of 26	ENSP00000264377.3	O75077-1
	ADAM23	ENST00000944282.1		c.433A>C	p.Ile145Leu	missense	Exon 2 of 26	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.361A>C	p.Ile121Leu	missense	Exon 2 of 27	ENSP00000614335.1

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000505 AC: 127 AN: 251342 AF XY: 0.000486

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000985

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000845 AC: 1235 AN: 1461848 Hom.: 1 Cov.: 31 AF XY: 0.000817 AC XY: 594 AN XY: 727222

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53406

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00107 AC: 1191 AN: 1111988

Other (OTH) AF: 0.000430 AC: 26 AN: 60396

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74486

African (AFR) AF: 0.000216 AC: 9 AN: 41574

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000738 Hom.: 1

Bravo AF: 0.000491

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000379 AC: 46

EpiCase AF: 0.000927

EpiControl AF: 0.00107

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.063
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-0.075	N
PhyloP100		2.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.037
Sift	Benign	0.68	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.36
MVP		0.093
MPC		0.054
ClinPred		0.0096	T
GERP RS		3.6
Varity_R		0.043
gMVP		0.35
Mutation Taster		=91/9	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: rs149165152; hg19: chr2-207310177;