rs1205610318

Variant names:

• chr4-140389234-C-A
• NM_004362.3:c.1823G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-140389234-C-A
• chr4-140389234-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004362.3(CLGN):​c.1823G>T​(p.Arg608Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,022 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. R608Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CLGN NM_004362.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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

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
CLGN	NM_004362.3	c.1823G>T	p.Arg608Leu	missense_variant	Exon 15 of 15	ENST00000325617.10	NP_004353.1
CLGN	NM_001130675.2	c.1823G>T	p.Arg608Leu	missense_variant	Exon 16 of 16		NP_001124147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLGN	ENST00000325617.10	c.1823G>T	p.Arg608Leu	missense_variant	Exon 15 of 15	1	NM_004362.3	ENSP00000326699.5
CLGN	ENST00000414773.5	c.1823G>T	p.Arg608Leu	missense_variant	Exon 16 of 16	1		ENSP00000392782.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460022 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726352

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;.
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.032	D;D
Polyphen		0.98	D;D
Vest4		0.43
MutPred		0.42		Loss of methylation at K604 (P = 0.0677);Loss of methylation at K604 (P = 0.0677);
MVP		0.69
MPC		0.42
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.18
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-141310388;