rs144153954

Variant names:

• chr19-1506032-G-A
• rs144153954
• NM_213604.3:c.1399C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-1506032-G-A
• chr19-1506032-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_213604.3(ADAMTSL5):​c.1399C>T​(p.Arg467Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,578,142 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (37 hom.)
• Consequence: ADAMTSL5 NM_213604.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.446
• Publications: 8 publications found

Genes affected

ADAMTSL5 (HGNC:27912): (ADAMTS like 5) Enables heparin binding activity and microfibril binding activity. Located in extracellular region and microfibril. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054112077).
• BP6: Variant 19-1506032-G-A is Benign according to our data. Variant chr19-1506032-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2648938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213604.3. 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
	ADAMTSL5	NM_213604.3	MANE Select	c.1399C>T	p.Arg467Trp	missense	Exon 12 of 12	NP_998769.2	X6R4H8
	ADAMTSL5	NM_001367197.1		c.1429C>T	p.Arg477Trp	missense	Exon 13 of 13	NP_001354126.1	Q6ZMM2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL5	ENST00000330475.9	TSL:2 MANE Select	c.1399C>T	p.Arg467Trp	missense	Exon 12 of 12	ENSP00000327608.3	X6R4H8
	ADAMTSL5	ENST00000585700.5	TSL:1	n.1397C>T		non_coding_transcript_exon	Exon 11 of 11
	ADAMTSL5	ENST00000590440.5	TSL:1	n.1437C>T		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes AF: 0.00518 AC: 789 AN: 152232 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00775

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00508 AC: 1032 AN: 203232 AF XY: 0.00494

Gnomad AFR exome AF: 0.00145

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00188

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.00713

Gnomad OTH exome AF: 0.00595

GnomAD4 exome AF: 0.00633 AC: 9020 AN: 1425792 Hom.: 37 Cov.: 31 AF XY: 0.00615 AC XY: 4350 AN XY: 707788

African (AFR) AF: 0.00100 AC: 33 AN: 32930

American (AMR) AF: 0.00335 AC: 139 AN: 41532

Ashkenazi Jewish (ASJ) AF: 0.00204 AC: 51 AN: 24994

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38848

South Asian (SAS) AF: 0.00379 AC: 313 AN: 82670

European-Finnish (FIN) AF: 0.0110 AC: 439 AN: 39816

Middle Eastern (MID) AF: 0.00533 AC: 25 AN: 4690

European-Non Finnish (NFE) AF: 0.00690 AC: 7594 AN: 1101216

Other (OTH) AF: 0.00719 AC: 425 AN: 59096

GnomAD4 genome AF: 0.00519 AC: 790 AN: 152350 Hom.: 2 Cov.: 33 AF XY: 0.00532 AC XY: 396 AN XY: 74500

African (AFR) AF: 0.00137 AC: 57 AN: 41594

American (AMR) AF: 0.00510 AC: 78 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4826

European-Finnish (FIN) AF: 0.00838 AC: 89 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00775 AC: 527 AN: 68030

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00586 Hom.: 1

Bravo AF: 0.00465

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00163 AC: 7

ESP6500EA AF: 0.00510 AC: 43

ExAC AF: 0.00467 AC: 557

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.45
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0020	D
Vest4		0.15
MVP		0.52
MPC		0.50
ClinPred		0.020	T
GERP RS		-2.5
gMVP		0.49
Mutation Taster		=100/0	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: rs144153954; hg19: chr19-1506031; COSMIC: COSV57861136; COSMIC: COSV57861136;