NM_001853.4:c.*319A>C

Variant names:

• chr20-62841051-A-C
• rs886056917
• NM_001853.4:c.*319A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001853.4(COL9A3):​c.*319A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL9A3 NM_001853.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

COL9A3 (HGNC:2219): (collagen type IX alpha 3 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. Mutations in this gene are associated with multiple epiphyseal dysplasia type 3. [provided by RefSeq, Jan 2010]

TCFL5 (HGNC:11646): (transcription factor like 5) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of transcription by RNA polymerase II; regulation of cell population proliferation; and spermatogenesis. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001853.4. 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
	COL9A3	NM_001853.4	MANE Select	c.*319A>C		3_prime_UTR	Exon 32 of 32	NP_001844.3
	TCFL5	NM_006602.4	MANE Select	c.*924T>G		3_prime_UTR	Exon 6 of 6	NP_006593.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	ENST00000649368.1	MANE Select	c.*319A>C		3_prime_UTR	Exon 32 of 32	ENSP00000496793.1	Q14050
	TCFL5	ENST00000335351.8	TSL:1 MANE Select	c.*924T>G		3_prime_UTR	Exon 6 of 6	ENSP00000334294.3	Q9UL49-3
	COL9A3	ENST00000467819.5	TSL:1	n.885A>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 196096 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 104992

African (AFR) AF: 0.00 AC: 0 AN: 5438

American (AMR) AF: 0.00 AC: 0 AN: 7450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5390

East Asian (EAS) AF: 0.00 AC: 0 AN: 9162

South Asian (SAS) AF: 0.00 AC: 0 AN: 31454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 116180

Other (OTH) AF: 0.00 AC: 0 AN: 10518

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Multiple Epiphyseal Dysplasia, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.52
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs886056917; hg19: chr20-61472403;