14-74097813-C-G

Variant names:

• chr14-74097813-C-G
• rs1402488470
• NM_001024674.3:c.152C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001024674.3(LIN52):​c.152C>G​(p.Pro51Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LIN52 NM_001024674.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73
• Publications: 0 publications found

Genes affected

LIN52 (HGNC:19856): (lin-52 DREAM MuvB core complex component) Predicted to be involved in transcription, DNA-templated. Predicted to be located in nucleoplasm. Predicted to be part of DRM complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC105370563 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28187025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024674.3. 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
	LIN52	NM_001024674.3	MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 4 of 6	NP_001019845.2	B3KN83
	LIN52	NM_001372005.1		c.152C>G	p.Pro51Arg	missense	Exon 4 of 6	NP_001358934.1
	LIN52	NM_001372006.1		c.146C>G	p.Pro49Arg	missense	Exon 4 of 6	NP_001358935.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN52	ENST00000555028.7	TSL:1 MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 4 of 6	ENSP00000451812.2	B3KN83
	LIN52	ENST00000962093.1		c.152C>G	p.Pro51Arg	missense	Exon 4 of 7	ENSP00000632152.1
	LIN52	ENST00000899706.1		c.170C>G	p.Pro57Arg	missense	Exon 4 of 6	ENSP00000569765.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460512 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726654

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110844

Other (OTH) AF: 0.00 AC: 0 AN: 60334

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000568638), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.7
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.31
Sift	Benign	0.047	D
Sift4G	Benign	0.11	T
Polyphen		0.071	B
Vest4		0.47
MutPred		0.57		Gain of catalytic residue at I50 (P = 0.0038)
MVP		0.33
MPC		0.56
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.75
Mutation Taster		=52/48	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: rs1402488470; hg19: chr14-74564516;