rs1422795

Variant names:

• chr5-157509356-T-C
• rs1422795
• NM_033274.5:c.850A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-157509356-T-C
• chr5-157509356-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033274.5(ADAM19):​c.850A>G​(p.Ser284Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,612,026 control chromosomes in the GnomAD database, including 110,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. S284C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.42 (14381 hom., cov: 33)
  • Exomes 𝑓: 0.36 (96592 hom.)
• Consequence: ADAM19 NM_033274.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 57 publications found

Genes affected

ADAM19 (HGNC:197): (ADAM metallopeptidase domain 19) 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. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.8602465E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033274.5. 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
	ADAM19	NM_033274.5	MANE Select	c.850A>G	p.Ser284Gly	missense	Exon 9 of 23	NP_150377.1	Q9H013-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000257527.9	TSL:1 MANE Select	c.850A>G	p.Ser284Gly	missense	Exon 9 of 23	ENSP00000257527.5	Q9H013-2
	ADAM19	ENST00000517905.1	TSL:5	c.850A>G	p.Ser284Gly	missense	Exon 9 of 22	ENSP00000428654.1	Q9H013-1
	ADAM19	ENST00000957644.1		c.850A>G	p.Ser284Gly	missense	Exon 9 of 23	ENSP00000627703.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63455 AN: 151962 Hom.: 14349 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.429

GnomAD2 exomes AF: 0.380 AC: 95007 AN: 250186 AF XY: 0.380

Gnomad AFR exome AF: 0.596

Gnomad AMR exome AF: 0.447

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.356 AC: 519671 AN: 1459946 Hom.: 96592 Cov.: 37 AF XY: 0.360 AC XY: 261153 AN XY: 726200

African (AFR) AF: 0.607 AC: 20290 AN: 33418

American (AMR) AF: 0.446 AC: 19864 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 11097 AN: 26094

East Asian (EAS) AF: 0.143 AC: 5691 AN: 39664

South Asian (SAS) AF: 0.478 AC: 41088 AN: 85936

European-Finnish (FIN) AF: 0.379 AC: 20239 AN: 53370

Middle Eastern (MID) AF: 0.423 AC: 2435 AN: 5760

European-Non Finnish (NFE) AF: 0.339 AC: 376394 AN: 1110876

Other (OTH) AF: 0.374 AC: 22573 AN: 60314

GnomAD4 genome AF: 0.418 AC: 63541 AN: 152080 Hom.: 14381 Cov.: 33 AF XY: 0.419 AC XY: 31143 AN XY: 74352

African (AFR) AF: 0.591 AC: 24511 AN: 41472

American (AMR) AF: 0.411 AC: 6290 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3472

East Asian (EAS) AF: 0.134 AC: 693 AN: 5172

South Asian (SAS) AF: 0.459 AC: 2211 AN: 4820

European-Finnish (FIN) AF: 0.383 AC: 4055 AN: 10576

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23049 AN: 67960

Other (OTH) AF: 0.429 AC: 907 AN: 2112

Alfa AF: 0.364 Hom.: 52594

Bravo AF: 0.428

TwinsUK AF: 0.340 AC: 1259

ALSPAC AF: 0.341 AC: 1315

ESP6500AA AF: 0.579 AC: 2552

ESP6500EA AF: 0.352 AC: 3024

ExAC AF: 0.382 AC: 46383

Asia WGS AF: 0.311 AC: 1082 AN: 3478

EpiCase AF: 0.344

EpiControl AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.000069	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.21
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.11	T
Sift4G	Benign	0.12	T
Polyphen		0.90	P
Vest4		0.070
MPC		0.49
ClinPred		0.016	T
GERP RS		1.3
Varity_R		0.12
gMVP		0.29
Mutation Taster		=99/1	polymorphism (auto)

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: rs1422795; hg19: chr5-156936364; COSMIC: COSV57425399;