19-49117927-G-A

Variant names:

• chr19-49117927-G-A
• rs569310243
• NM_022165.3:c.511G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022165.3(LIN7B):​c.511G>A​(p.Val171Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V171L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIN7B NM_022165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

LIN7B (HGNC:17788): (lin-7 homolog B, crumbs cell polarity complex component) Enables protein domain specific binding activity. Predicted to be involved in maintenance of epithelial cell apical/basal polarity; neurotransmitter secretion; and protein localization to basolateral plasma membrane. Predicted to be located in plasma membrane. Predicted to be part of MPP7-DLG1-LIN7 complex. Predicted to be active in basolateral plasma membrane; cell-cell junction; and synapse. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000297778 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022165.3. 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
	LIN7B	NM_022165.3	MANE Select	c.511G>A	p.Val171Ile	missense	Exon 5 of 6	NP_071448.1	Q9HAP6-1
	LIN7B	NM_001308419.2		c.301G>A	p.Val101Ile	missense	Exon 4 of 5	NP_001295348.1	Q9HAP6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN7B	ENST00000221459.7	TSL:1 MANE Select	c.511G>A	p.Val171Ile	missense	Exon 5 of 6	ENSP00000221459.2	Q9HAP6-1
	LIN7B	ENST00000882750.1		c.439G>A	p.Val147Ile	missense	Exon 4 of 5	ENSP00000552809.1
	LIN7B	ENST00000391864.7	TSL:3	c.301G>A	p.Val101Ile	missense	Exon 4 of 5	ENSP00000375737.3	Q9HAP6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.0	L
PhyloP100		8.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.076	T
Polyphen		0.93	P
Vest4		0.63
MutPred		0.49		Loss of disorder (P = 0.0644)
MVP		0.56
MPC		1.3
ClinPred		0.94	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.21
Mutation Taster		=75/25	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: rs569310243; hg19: chr19-49621184;