19-1506602-C-A

Variant names:

• chr19-1506602-C-A
• rs746736830
• NM_213604.3:c.1102G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213604.3(ADAMTSL5):​c.1102G>T​(p.Gly368Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G368S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTSL5 NM_213604.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1102G>T	p.Gly368Cys	missense	Exon 11 of 12	NP_998769.2	X6R4H8
	ADAMTSL5	NM_001367197.1		c.1132G>T	p.Gly378Cys	missense	Exon 12 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.1102G>T	p.Gly368Cys	missense	Exon 11 of 12	ENSP00000327608.3	X6R4H8
	ADAMTSL5	ENST00000590440.5	TSL:1	n.1140G>T		non_coding_transcript_exon	Exon 11 of 12
	ADAMTSL5	ENST00000585700.5	TSL:1	n.1120+137G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459698 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725824

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 85572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111424

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000161 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.0
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.097
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.035	D
Vest4		0.53
MutPred		0.47		Loss of loop (P = 0.0374)
MVP		0.44
MPC		0.48
ClinPred		0.97	D
GERP RS		-2.1
gMVP		0.46
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746736830; hg19: chr19-1506601;