chr4-140395849-T-G

Variant names:

• chr4-140395849-T-G
• rs377332621
• NM_004362.3:c.1119A>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.1119A>C​(p.Arg373Ser) 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. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLGN NM_004362.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• 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=0.15817973).

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.1119A>C	p.Arg373Ser	missense	Exon 10 of 15	NP_004353.1	A0A140VKG2
	CLGN	NM_001130675.2		c.1119A>C	p.Arg373Ser	missense	Exon 11 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.1119A>C	p.Arg373Ser	missense	Exon 10 of 15	ENSP00000326699.5	O14967-1
	CLGN	ENST00000414773.5	TSL:1	c.1119A>C	p.Arg373Ser	missense	Exon 11 of 16	ENSP00000392782.1	O14967-1
	CLGN	ENST00000897460.1		c.1119A>C	p.Arg373Ser	missense	Exon 10 of 15	ENSP00000567519.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.070	N
PhyloP100		0.014
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.091
Sift	Benign	0.38	T
Sift4G	Benign	0.24	T
Polyphen		0.0090	B
Vest4		0.17
MutPred		0.56		Gain of ubiquitination at K369 (P = 0.0337)
MVP		0.32
MPC		0.11
ClinPred		0.21	T
GERP RS		-1.5
Varity_R		0.19
gMVP		0.40
Mutation Taster		=75/25	polymorphism

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: rs377332621; hg19: chr4-141317003;