NM_022165.3:c.47G>T

Variant names:

• chr19-49114858-G-T
• rs1172035904
• NM_022165.3:c.47G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022165.3(LIN7B):​c.47G>T​(p.Arg16Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R16Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIN7B NM_022165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.28
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

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.47G>T	p.Arg16Leu	missense	Exon 2 of 6	NP_071448.1	Q9HAP6-1
	LIN7B	NM_001308419.2		c.47G>T	p.Arg16Leu	missense	Exon 2 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.47G>T	p.Arg16Leu	missense	Exon 2 of 6	ENSP00000221459.2	Q9HAP6-1
	LIN7B	ENST00000882750.1		c.47G>T	p.Arg16Leu	missense	Exon 2 of 5	ENSP00000552809.1
	LIN7B	ENST00000391864.7	TSL:3	c.47G>T	p.Arg16Leu	missense	Exon 2 of 5	ENSP00000375737.3	Q9HAP6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 105398 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1306122 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 643150

African (AFR) AF: 0.00 AC: 0 AN: 26404

American (AMR) AF: 0.00 AC: 0 AN: 24288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21002

East Asian (EAS) AF: 0.00 AC: 0 AN: 30946

South Asian (SAS) AF: 0.00 AC: 0 AN: 69004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3808

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041286

Other (OTH) AF: 0.00 AC: 0 AN: 53280

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.3
PrimateAI	Pathogenic	0.96	D
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.79
MutPred		0.67		Loss of MoRF binding (P = 0.0483)
MVP		0.58
MPC		1.5
ClinPred		0.99	D
GERP RS		2.9
PromoterAI		-0.0059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.81
Mutation Taster		=26/74	disease causing

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: rs1172035904; hg19: chr19-49618115;