11-27501879-T-C

Position:

• chr11-27501879-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000278193.7(LIN7C):​c.79A>G​(p.Ser27Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LIN7C ENST00000278193.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.210989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN7C	NM_018362.4	c.79A>G	p.Ser27Gly	missense_variant	2/5	ENST00000278193.7	NP_060832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN7C	ENST00000278193.7	c.79A>G	p.Ser27Gly	missense_variant	2/5	1	NM_018362.4	ENSP00000278193.2
LIN7C	ENST00000524596.1	c.79A>G	p.Ser27Gly	missense_variant	2/4	1		ENSP00000435353.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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 07, 2023

The c.79A>G (p.S27G) alteration is located in exon 2 (coding exon 2) of the LIN7C gene. This alteration results from a A to G substitution at nucleotide position 79, causing the serine (S) at amino acid position 27 to be replaced by a glycine (G). 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	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D
Eigen	Benign	0.064
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.056
Sift	Benign	0.060	T;D
Sift4G	Benign	0.064	T;T
Polyphen		0.0010	B;B
Vest4		0.26
MutPred		0.44		Loss of phosphorylation at S27 (P = 0.0245);Loss of phosphorylation at S27 (P = 0.0245);
MVP		0.47
MPC		0.56
ClinPred		0.89	D
GERP RS		5.6
Varity_R		0.38
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27523426;