11-27498708-C-T

Position:

• chr11-27498708-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018362.4(LIN7C):​c.535G>A​(p.Glu179Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIN7C NM_018362.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

Genes affected

LIN7C (HGNC:17789): (lin-7 homolog C, crumbs cell polarity complex component) Enables L27 domain binding activity and cytoskeletal protein binding activity. Involved in morphogenesis of an epithelial sheet. Located in cell-cell junction; cytoplasm; and plasma membrane. Part of MPP7-DLG1-LIN7 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN7C	NM_018362.4	c.535G>A	p.Glu179Lys	missense_variant	5/5	ENST00000278193.7	NP_060832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN7C	ENST00000278193.7	c.535G>A	p.Glu179Lys	missense_variant	5/5	1	NM_018362.4	ENSP00000278193	P1
LIN7C	ENST00000524596.1	c.463G>A	p.Glu155Lys	missense_variant	4/4	1		ENSP00000435353

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2023

The c.535G>A (p.E179K) alteration is located in exon 5 (coding exon 5) of the LIN7C gene. This alteration results from a G to A substitution at nucleotide position 535, causing the glutamic acid (E) at amino acid position 179 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.99	D;D
Vest4		0.69
MutPred		0.33		Gain of methylation at E179 (P = 0.0024);.;
MVP		0.84
MPC		1.4
ClinPred		0.97	D
GERP RS		6.2
Varity_R		0.52
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27520255;