NM_001024674.3:c.107C>T

Variant names:

• chr14-74095960-C-T
• rs532558275
• NM_001024674.3:c.107C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001024674.3(LIN52):​c.107C>T​(p.Ala36Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,608,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LIN52 NM_001024674.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030426085).

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.107C>T	p.Ala36Val	missense	Exon 3 of 6	NP_001019845.2	B3KN83
	LIN52	NM_001372005.1		c.107C>T	p.Ala36Val	missense	Exon 3 of 6	NP_001358934.1
	LIN52	NM_001372006.1		c.101C>T	p.Ala34Val	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.107C>T	p.Ala36Val	missense	Exon 3 of 6	ENSP00000451812.2	B3KN83
	LIN52	ENST00000962093.1		c.107C>T	p.Ala36Val	missense	Exon 3 of 7	ENSP00000632152.1
	LIN52	ENST00000899706.1		c.125C>T	p.Ala42Val	missense	Exon 3 of 6	ENSP00000569765.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152138 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000888 AC: 22 AN: 247666 AF XY: 0.0000747

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00106

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1456496 Hom.: 0 Cov.: 27 AF XY: 0.0000193 AC XY: 14 AN XY: 724628

African (AFR) AF: 0.00 AC: 0 AN: 33204

American (AMR) AF: 0.00 AC: 0 AN: 44240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.000329 AC: 13 AN: 39462

South Asian (SAS) AF: 0.0000819 AC: 7 AN: 85422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108934

Other (OTH) AF: 0.0000166 AC: 1 AN: 60146

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152256 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74442

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Benign	0.33
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.025
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.76	N
PhyloP100		5.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.056
Sift	Benign	0.21	T
Sift4G	Benign	0.14	T
Polyphen		0.0020	B
Vest4		0.27
MVP		0.068
MPC		1.0
ClinPred		0.12	T
GERP RS		5.7
Varity_R		0.14
gMVP		0.58
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs532558275; hg19: chr14-74562663;