rs1177811521

Variant names:

• chr14-74095979-C-G
• rs1177811521
• NM_001024674.3:c.126C>G

Variant summary

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

The NM_001024674.3(LIN52):​c.126C>G​(p.Phe42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,456,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: LIN52 NM_001024674.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18
• 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]

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=0.07303849).

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.126C>G	p.Phe42Leu	missense	Exon 3 of 6	NP_001019845.2	B3KN83
	LIN52	NM_001372005.1		c.126C>G	p.Phe42Leu	missense	Exon 3 of 6	NP_001358934.1
	LIN52	NM_001372006.1		c.120C>G	p.Phe40Leu	missense	Exon 3 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.126C>G	p.Phe42Leu	missense	Exon 3 of 6	ENSP00000451812.2	B3KN83
	LIN52	ENST00000962093.1		c.126C>G	p.Phe42Leu	missense	Exon 3 of 7	ENSP00000632152.1
	LIN52	ENST00000899706.1		c.144C>G	p.Phe48Leu	missense	Exon 3 of 6	ENSP00000569765.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247442 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000254 AC: 37 AN: 1456020 Hom.: 0 Cov.: 27 AF XY: 0.0000235 AC XY: 17 AN XY: 724444

African (AFR) AF: 0.00 AC: 0 AN: 33130

American (AMR) AF: 0.00 AC: 0 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00 AC: 0 AN: 85306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000325 AC: 36 AN: 1108738

Other (OTH) AF: 0.00 AC: 0 AN: 60124

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000935 Hom.: 0

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	0.86
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.49	N
PhyloP100		2.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.27
Sift	Benign	0.68	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.37
MutPred		0.31		Gain of catalytic residue at K47 (P = 2e-04)
MVP		0.19
MPC		1.6
ClinPred		0.51	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.58
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs1177811521; hg19: chr14-74562682;