rs1422795

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM19	NM_033274.5	c.850A>G	p.Ser284Gly	missense_variant	9/23	ENST00000257527.9	NP_150377.1
ADAM19	XM_047417858.1	c.850A>G	p.Ser284Gly	missense_variant	9/22		XP_047273814.1
ADAM19	XM_047417859.1	c.49A>G	p.Ser17Gly	missense_variant	2/16		XP_047273815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000257527.9	c.850A>G	p.Ser284Gly	missense_variant	9/23	1	NM_033274.5	ENSP00000257527	P1
ADAM19	ENST00000517905.1	c.850A>G	p.Ser284Gly	missense_variant	9/22	5		ENSP00000428654
ADAM19	ENST00000517951.5	c.*41A>G		3_prime_UTR_variant, NMD_transcript_variant	9/23	2		ENSP00000428376

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

GnomAD3 exomes AF: 0.380 AC: 95007 AN: 250186 Hom.: 19371 AF XY: 0.380 AC XY: 51420 AN XY: 135222

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 SAS exome AF: 0.478

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

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.374

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

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.429

Alfa AF: 0.358 Hom.: 26574

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 v4.3

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;T
MetaRNN	Benign	0.000069	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.93	P;P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.10
Sift	Benign	0.11	T;T
Sift4G	Benign	0.12	T;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

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