NM_213604.3:c.974G>C

Variant names:

• chr19-1506807-C-G
• rs777151542
• NM_213604.3:c.974G>C

Variant summary

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

The NM_213604.3(ADAMTSL5):​c.974G>C​(p.Arg325Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000504 in 1,389,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R325Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ADAMTSL5 NM_213604.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• Publications: 1 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.974G>C	p.Arg325Pro	missense	Exon 10 of 12	NP_998769.2	X6R4H8
	ADAMTSL5	NM_001367197.1		c.1004G>C	p.Arg335Pro	missense	Exon 11 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.974G>C	p.Arg325Pro	missense	Exon 10 of 12	ENSP00000327608.3	X6R4H8
	ADAMTSL5	ENST00000585700.5	TSL:1	n.1052G>C		non_coding_transcript_exon	Exon 10 of 11
	ADAMTSL5	ENST00000590440.5	TSL:1	n.1012G>C		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000702 AC: 1 AN: 142386 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000131

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000504 AC: 7 AN: 1389168 Hom.: 0 Cov.: 36 AF XY: 0.00000584 AC XY: 4 AN XY: 685406

African (AFR) AF: 0.00 AC: 0 AN: 31074

American (AMR) AF: 0.00 AC: 0 AN: 31968

Ashkenazi Jewish (ASJ) AF: 0.0000408 AC: 1 AN: 24480

East Asian (EAS) AF: 0.0000557 AC: 2 AN: 35888

South Asian (SAS) AF: 0.00 AC: 0 AN: 78522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5278

European-Non Finnish (NFE) AF: 0.00000372 AC: 4 AN: 1076236

Other (OTH) AF: 0.00 AC: 0 AN: 57454

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.0045
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.33	T
PhyloP100		0.57
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.24
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.014	D
Vest4		0.45
MVP		0.62
MPC		0.47
ClinPred		0.95	D
GERP RS		3.0
gMVP		0.50
Mutation Taster		=67/33	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: rs777151542; hg19: chr19-1506806;