7-55366036-C-T

Variant names:

• chr7-55366036-C-T
• rs148273248
• NM_018697.4:c.11C>T

Variant summary

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

The NM_018697.4(LANCL2):​c.11C>T​(p.Thr4Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,488,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: LANCL2 NM_018697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.951
• Publications: 0 publications found

Genes affected

LANCL2 (HGNC:6509): (LanC like glutathione S-transferase 2) Enables phosphatidylinositol-3-phosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of transcription, DNA-templated and positive regulation of abscisic acid-activated signaling pathway. Located in several cellular components, including cortical actin cytoskeleton; cytosol; and nucleoplasm. [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=0.039365143).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018697.4. 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
	LANCL2	NM_018697.4	MANE Select	c.11C>T	p.Thr4Ile	missense	Exon 1 of 9	NP_061167.1	Q9NS86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL2	ENST00000254770.3	TSL:1 MANE Select	c.11C>T	p.Thr4Ile	missense	Exon 1 of 9	ENSP00000254770.2	Q9NS86
	LANCL2	ENST00000952390.1		c.11C>T	p.Thr4Ile	missense	Exon 1 of 10	ENSP00000622449.1
	LANCL2	ENST00000952391.1		c.11C>T	p.Thr4Ile	missense	Exon 1 of 9	ENSP00000622450.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152216 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000235 AC: 3 AN: 127492 AF XY: 0.00

Gnomad AFR exome AF: 0.000484

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000973 AC: 13 AN: 1335922 Hom.: 0 Cov.: 30 AF XY: 0.00000917 AC XY: 6 AN XY: 654528

African (AFR) AF: 0.000257 AC: 7 AN: 27230

American (AMR) AF: 0.0000716 AC: 2 AN: 27928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22088

East Asian (EAS) AF: 0.00 AC: 0 AN: 31612

South Asian (SAS) AF: 0.0000272 AC: 2 AN: 73636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5408

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045376

Other (OTH) AF: 0.0000366 AC: 2 AN: 54668

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152334 Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5 AN XY: 74496

African (AFR) AF: 0.000433 AC: 18 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.000460 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000338 AC: 4

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	0.22
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.95
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.025
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.057	T
Polyphen		0.58	P
Vest4		0.19
MVP		0.15
MPC		0.33
ClinPred		0.40	T
GERP RS		4.5
Varity_R		0.17
gMVP		0.53
Mutation Taster		=77/23	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: rs148273248; hg19: chr7-55433729;