chr12-80845798-G-A

Position:

• chr12-80845798-G-A

Variant summary

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

The NM_004664.4(LIN7A):​c.415C>T​(p.Pro139Ser) 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: LIN7A NM_004664.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

LIN7A (HGNC:17787): (lin-7 homolog A, crumbs cell polarity complex component) The protein encoded by this gene is involved in generating and maintaining the asymmetric distribution of channels and receptors at the cell membrane. The encoded protein also is required for the localization of some specific channels and can be part of a protein complex that couples synaptic vesicle exocytosis to cell adhesion in the brain. [provided by RefSeq, May 2016]

LIN7A (HGNC:):

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
LIN7A	NM_004664.4	c.415C>T	p.Pro139Ser	missense_variant	4/6	ENST00000552864.6	NP_004655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN7A	ENST00000552864.6	c.415C>T	p.Pro139Ser	missense_variant	4/6	1	NM_004664.4	ENSP00000447488.1

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

Feb 09, 2023

The c.415C>T (p.P139S) alteration is located in exon 4 (coding exon 4) of the LIN7A gene. This alteration results from a C to T substitution at nucleotide position 415, causing the proline (P) at amino acid position 139 to be replaced by a serine (S). 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	0.80
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;.
Vest4		0.84
MutPred		0.56		Gain of catalytic residue at P139 (P = 0);.;
MVP		0.75
MPC		0.95
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.42
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs866830191; hg19: chr12-81239577; COSMIC: COSV54020298;