Genetic Variant NM_213604.3:c.974G>C (chr19-1506807-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ADAMTSL5
NM_213604.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.573

Variant links:

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]

ADAMTSL5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL5	NM_213604.3 link	c.974G>C	p.Arg325Pro	missense_variant	Exon 10 of 12	ENST00000330475.9	NP_998769.2	Q6ZMM2Q0VD77X6R4H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL5	ENST00000330475.9 link	c.974G>C	p.Arg325Pro	missense_variant	Exon 10 of 12	2	NM_213604.3	ENSP00000327608.3		X6R4H8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000702

AC:

AN:

142386

Hom.:

AF XY:

0.00

AC XY:

AN XY:

76414

show subpopulations

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 SAS 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:

AN:

1389168

Hom.:

Cov.:

AF XY:

0.00000584

AC XY:

AN XY:

685406

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000408

Gnomad4 EAS exome

AF:

0.0000557

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000372

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;.

Eigen

Benign

0.0045

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.78

T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-0.33

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

D;D;.

REVEL

Benign

0.24

Sift

Uncertain

0.018

D;D;.

Sift4G

Uncertain

0.014

D;D;.

Vest4

0.45

MVP

0.62

MPC

0.47

ClinPred

0.95

GERP RS

3.0

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over