4-140396131-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_004362.3(CLGN):​c.959A>G​(p.Lys320Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

CLGN
NM_004362.3 missense

Scores

2
17

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.83
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-140396131-T-C is Pathogenic according to our data. Variant chr4-140396131-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 599571.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.11074209). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CLGNNM_004362.3 linkuse as main transcriptc.959A>G p.Lys320Arg missense_variant 9/15 ENST00000325617.10 NP_004353.1
CLGNNM_001130675.2 linkuse as main transcriptc.959A>G p.Lys320Arg missense_variant 10/16 NP_001124147.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLGNENST00000325617.10 linkuse as main transcriptc.959A>G p.Lys320Arg missense_variant 9/151 NM_004362.3 ENSP00000326699 P1O14967-1
CLGNENST00000414773.5 linkuse as main transcriptc.959A>G p.Lys320Arg missense_variant 10/161 ENSP00000392782 P1O14967-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Short stature Pathogenic:1
Likely pathogenic, no assertion criteria providedcase-controlInstitute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-NürnbergNov 18, 2001- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.081
T;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.81
T;.
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.87
L;L
MutationTaster
Benign
0.97
N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.066
Sift
Benign
0.043
D;D
Sift4G
Benign
0.15
T;T
Polyphen
0.040
B;B
Vest4
0.12
MutPred
0.44
Loss of methylation at K320 (P = 7e-04);Loss of methylation at K320 (P = 7e-04);
MVP
0.42
MPC
0.080
ClinPred
0.32
T
GERP RS
0.34
Varity_R
0.11
gMVP
0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1560739587; hg19: chr4-141317285; API