rs34570487

Variant names:

• chr15-88855595-A-C
• NM_001369268.1:c.3010A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-88855595-A-C
• chr15-88855595-A-G
• chr15-88855595-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001369268.1(ACAN):​c.3010A>C​(p.Thr1004Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1004A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACAN NM_001369268.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

Genes affected

ACAN (HGNC:319): (aggrecan) This gene is a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage. Mutations in this gene may be involved in skeletal dysplasia and spinal degeneration. Multiple alternatively spliced transcript variants that encode different protein isoforms have been observed in this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10686171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAN	NM_001369268.1	c.3010A>C	p.Thr1004Pro	missense_variant	Exon 12 of 19	ENST00000560601.4	NP_001356197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAN	ENST00000560601.4	c.3010A>C	p.Thr1004Pro	missense_variant	Exon 12 of 19	3	NM_001369268.1	ENSP00000453581.2

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000123 AC: 24 AN: 194586 Hom.: 0 Cov.: 0 AF XY: 0.000143 AC XY: 15 AN XY: 105262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000208

Gnomad4 EAS exome AF: 0.0000624

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000227

Gnomad4 NFE exome AF: 0.000176

Gnomad4 OTH exome AF: 0.0000984

GnomAD4 genome Cov.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.71
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.41	T;T;T;T;T;.
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Uncertain	0.053	D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.0	.;N;.;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0060	.;D;.;D;D;D
Sift4G	Benign	0.25	.;T;T;T;T;T
Vest4		0.058, 0.10, 0.068, 0.054, 0.059
MutPred		0.32		Loss of glycosylation at T1004 (P = 0.0247);Loss of glycosylation at T1004 (P = 0.0247);.;Loss of glycosylation at T1004 (P = 0.0247);Loss of glycosylation at T1004 (P = 0.0247);Loss of glycosylation at T1004 (P = 0.0247);
MVP		0.12
MPC		0.26
ClinPred		0.20	T
GERP RS		-1.5
Varity_R		0.10
gMVP		0.053

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-89398826;