14-74097813-C-A

Variant names:

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

Variant summary

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

The NM_001024674.3(LIN52):​c.152C>A​(p.Pro51His) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,512 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. P51R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LIN52 NM_001024674.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Pro51His	missense	Exon 4 of 6	NP_001019845.2	B3KN83
	LIN52	NM_001372005.1		c.152C>A	p.Pro51His	missense	Exon 4 of 6	NP_001358934.1
	LIN52	NM_001372006.1		c.146C>A	p.Pro49His	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>A	p.Pro51His	missense	Exon 4 of 6	ENSP00000451812.2	B3KN83
	LIN52	ENST00000962093.1		c.152C>A	p.Pro51His	missense	Exon 4 of 7	ENSP00000632152.1
	LIN52	ENST00000899706.1		c.170C>A	p.Pro57His	missense	Exon 4 of 6	ENSP00000569765.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251322 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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460512 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726654

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: 0.00 AC: 0 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: 9.00e-7 AC: 1 AN: 1110844

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.032	D
Polyphen		0.99	D
Vest4		0.57
MutPred		0.56		Gain of catalytic residue at I50 (P = 0.0038)
MVP		0.18
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.71
Mutation Taster		=48/52	disease causing

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;