rs1728790336

Variant names:

• chr4-140392350-T-G
• rs1728790336
• NM_004362.3:c.1520A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004362.3(CLGN):​c.1520A>C​(p.Lys507Thr) variant causes a missense 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: 32)
• Consequence: CLGN NM_004362.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

CLGN (HGNC:2060): (calmegin) Calmegin is a testis-specific endoplasmic reticulum chaperone protein. CLGN may play a role in spermatogeneisis and infertility. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21725234).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004362.3. 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
	CLGN	NM_004362.3	MANE Select	c.1520A>C	p.Lys507Thr	missense	Exon 13 of 15	NP_004353.1	A0A140VKG2
	CLGN	NM_001130675.2		c.1520A>C	p.Lys507Thr	missense	Exon 14 of 16	NP_001124147.1	O14967-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLGN	ENST00000325617.10	TSL:1 MANE Select	c.1520A>C	p.Lys507Thr	missense	Exon 13 of 15	ENSP00000326699.5	O14967-1
	CLGN	ENST00000414773.5	TSL:1	c.1520A>C	p.Lys507Thr	missense	Exon 14 of 16	ENSP00000392782.1	O14967-1
	CLGN	ENST00000897460.1		c.1520A>C	p.Lys507Thr	missense	Exon 13 of 15	ENSP00000567519.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
PhyloP100		1.6
Varity_R		0.32
gMVP		0.44
Mutation Taster		=50/50

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1728790336; hg19: chr4-141313504;